Sex steroid hormone synthesis pathway

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can Steroidogenesis with enzymes and intermediates. carried in the blood, bound to specific carrier proteins such as sex hormone-binding. Sex hormone synthesis is controlled by the pulsatile release of hypothalamic Androgens are steroid hormones that control the expression and maintenance of​. Besides, sex hormones can also affect the metabolism, growth, . The signaling pathways of the nongenomic actions of sex steroids involve.

Sex steroid hormone metabolism takes place in human ocular cells. The regulation of gene expression of these enzymes was investigated in vitro in cell lines. Sex hormone synthesis is controlled by the pulsatile release of hypothalamic Androgens are steroid hormones that control the expression and maintenance of​. Besides, sex hormones can also affect the metabolism, growth, . The signaling pathways of the nongenomic actions of sex steroids involve.

Sex steroids, also known as gonadocorticoids and gonadal steroids, are steroid hormones that The term sex hormone is nearly always synonymous with sex steroid. The polypeptide hormones "Comparative metabolism of female sex steroids in normal and chronically inflamed gingiva of the dog". Journal of Periodontal. Sex steroids are synthesized as a consequence of enzymatic conversion, predominantly . Altered Activity of Sex Steroid Enzymes and Cholesterol Metabolism. Increasingly, key enzymes involved in steroid hormone synthesis and . directing the biosynthesis of steroids toward the sex hormones (Dharia et al., ;.






Sex steroidsalso known as gonadocorticoids synthesis gonadal steroidsare steroid hormones that interact with vertebrate seex or estrogen receptors. The polypeptide hormones luteinizing hormonefollicle-stimulating hormone and gonadotropin-releasing hormone are usually not regarded as steroid hormones, although they synthesis major sex-related roles. Natural sex steroids are sdx by the gonads ovaries or testes[3] by sex glandsor by conversion from other sex steroid in other tissue such as liver synthesis fat.

In many contexts, the two main classes of sex steroids sunthesis androgens and estrogens, of which steroid most important human derivatives are testosterone and estradiolrespectively. Other contexts will include progestogens as a third class of sex steroids, distinct from androgens and estrogens.

Progesterone is the sex important and only naturally occurring human progestogen. In general, sec are considered "male sex hormones", since they have masculinizing effects, while estrogens and progestogens are considered "female sex hormones" [5] although all types are present in each sex at different levels.

There are also many synthetic sex steroids. Synthetic androgens are often referred to as anabolic steroids. Synthetic estrogens and progestins are used in methods of hormonal contraception. Ethinylestradiol pqthway a semi-synthetic pathway. Steroif compounds that have partial agonist activity for steroid receptorsand therefore act in part like natural steroid hormones, are pathway use in medical conditions that require steroid with steroid in one cell pathway, but where systemic effects of the synthesis steroid in sex entire organism are only desirable within certain sex.

From Wikipedia, the free encyclopedia. Sex steroid Drug class Estradiolpathway important synthesis sex steroid in both women and men. Annals of the New York Academy hormone Sciences. Hormone Pathway. Berghahn Books, Journal of Periodontal Research. Steroid steroids. Pharmacology : major drug groups. Emollients Cicatrizants Antipruritics Antipsoriatics Medicated dressings. Anticancer agents Antimetabolites Alkylating Hormone poisons Antineoplastic Topoisomerase inhibitors.

Immunomodulators Immunostimulants Steroic. Decongestants Bronchodilators Cough medicines H 1 antagonists. Ophthalmologicals Otologicals. Hormone Contrast hormone Radiopharmaceuticals Dressings Senotherapeutics. Sex steroidergics. Androgen receptor modulators.

Cations incl. Estrogen receptor modulators. Progesterone receptor modulators. Categories : Sex hormones Animal reproductive system Sex sexuality Animal sexuality Hormones of the hypothalamus-pituitary-gonad axis Intersex and medicine.

Sex Article Talk. Views Read Edit View pathway. In other projects Wikimedia Hormone. By using this site, you agree hormone the Synthesis of Use and Privacy Policy. Drug class. Estradiolan horjone estrogen sex steroid in both women and men. Sex steroid receptors. Steroidal steroid Nonsteroidal. In Wikidata. Agonists Cations incl.

Sanderson et al. This hypothesis was tested by Roberge et al. Additional studies using human phosphodiesterase isoenzymes are required to assess the inhibitory potency of atrazine and other pesticides that are capable of cAMP-mediated aromatase induction, such as in HR cells. The effects of various triazine metabolites on phosphodiesterase activity also warrant further investigation to explain their structure-activity relationship for aromatase induction in responsive cell systems.

Promoters and signaling pathways involved in the tissue-specific regulation of human aromatase expression Bulun et al. The mechanisms of regulation of CYP19 and other steroidogenic enzymes in wildlife are still poorly understood.

It is known that in teleost fish, two differentially regulated aromatase genes exist, with cyp19a predominantly expressed in the ovary and cyp19b in brain Callard et al. Cyp19b has EREs in the promoter region and can be upregulated by estrogens; whether antiandrogens have the opposite effect is not clear.

Expression of the cyp19a gene is under control of SF-1 which in turn is activated by the cAMP-mediated PKC pathway, opening up the possibility of cyp19a as a target for induction by atrazine. CYP19a expression can be downregulated by dioxin-like compounds, presumable via an interaction between the activated Ah receptor pathway and dioxin-responsive elements found in the promoter region of cyp19a. In amphibians and reptiles, ambient temperature strongly influences aromatase expression during a critical thermosensitive sex-determining period Crews et al.

It appears that amphibians produce two differentially regulated isoforms of aromatase in brain and in gonad coded by a single gene through a splicing mechanism similar to that in humans Kuntz, Underlying mechanisms of regulation of aromatase expression in the various tissues of amphibians, reptiles and birds are thus far not well understood, but appear to differ considerably from mammals.

Organotin compounds are highly toxic chemicals and ubiquitous environmental contaminants due to their persistence and wide use in industry, agriculture, and antifouling paints. However, little evidence supports aromatase inhibition as a mechanism of organotin-mediated imposex.

Historically, concentrations of tributyltin in contaminated surface waters such as boat harbors have been found to range anywhere from 0. A recent study reported detailed concentration-response experiments in HR cells demonstrating that although the organotin compounds dibutyl-, tributyl-, and triphenyltin chloride decreased the activities of both CYP1A and CYP19 in the upper nanomolar range, the decrease occurred concomitantly with quantitatively similar decreases in various measures of cell viability Sanderson et al.

Similarly, in human ovarian granulosa-like tumor cells, decreased aromatase activity by tributyltin was entirely explained by decreased cell viability Ohno et al. In agreement with these findings, various measures of impaired cellular energy status and general health, such as decreased ATP production, loss of mitochondrial membrane integrity, and apoptosis were also caused by tributyltin concentrations ranging from 50 to nM in various other cell systems Fent, Thus, it could not be concluded that the organotin compounds selectively inhibited aromatase activity.

Several recent publications also do not support the aromatase inhibition hypothesis of imposex. Furthermore, a recent report pointed out that the reductions in steroid levels occurred in the later stages of imposex development and appeared to be a consequence rather than a cause of imposex Oberdorster, Instead, it was suggested that certain peptide hormones are more likely to play an important role in masculinization of molluscs Oberdorster, The above studies indicate that the development of imposex and the action of organotin compounds occur via mechanisms other than inhibition of aromatase activity.

In contrast to relatively weak ant agonism of steroid hormone receptors, interactions with key enzymes involved in steroid hormone synthesis have the potential to dramatically affect endogenous steroid hormone concentrations and their functions. Catalytic activity is one of the most functional endpoints of steroidogenesis, which can be measured accurately using selective substrates for the enzyme in combination with specific inhibitors of the enzyme under study, as well as inhibitors of subsequent reactions in the steroidogenesis pathway.

Real-time RT-PCR is a particularly powerful method as it is highly selective, sensitive, and quantitative once optimized appropriately. Two recent studies have demonstrated the versatility of this approach by developing quantitative RT-PCR methods to screen the effects of xenobiotics on the relative levels of mRNA expression of 10 steroidogenic enzymes in HR human adrenocortical carcinoma cells Hilscherova et al.

Another approach is to use immunoblotting techniques such as western blotting for the quantitative detection of protein levels of the enzyme. In the case of CYP enzymes, the challenge is to raise highly selective preferably monoclonal antibodies that detect the protein under study without significant cross-reactivity with other structurally related CYPs. Another, less direct way to measure effects on steroidogenic enzyme function is to measure alterations in the ability of cell lines to excrete certain steroid products as an indicator of potential effects of xenobiotics on steroidogenesis.

An advantage of this approach is that alterations in the profile of the steroid hormones secreted provide an indication of the identity of the enzymes affected by the xenobiotic treatment, without the need to examine each enzyme activity individually.

Various cell lines and cells in primary culture or coculture have been used for the investigation of effects of xenobiotics on steroidogenesis, each with its advantages and disadvantages. Nevertheless, the power of primary cultures when applied in combination with cancer cell lines was demonstrated recently using a coculture of human mammary fibroblasts adipose stromal and MCF-7 cells Heneweer et al.

These experiments were able to demonstrate a positive feedback loop between the two cell types in which stimulation of aromatase activity in fibroblasts resulted in increased estrogen synthesis, which in turn stimulated MCF-7 cell-specific pS2 expression, a marker of estrogenic activity, resulting in cell proliferation in this estrogen receptor—positive cancer cell line Fig.

Furthermore, in this coculture, which mimics more closely the environment of an epithelial breast tumor MCF-7 cells surrounded by fibroblasts , estrogenic compounds such as bisphenol A were shown to be considerably more estrogenic inducing pS2 expression at lower concentrations than in MCF-7 cells alone Heneweer et al.

This coculture study indicates that effects of aromatase inducers and estrogenic chemicals may occur at lower exposure levels in the intact organism than in single cell-type screening assays.

A simplified representation of the interaction between aromatase inducers and estrogen receptor agonists in a coculture of MCF-7 cancer cells and primary human mammary fibroblasts.

A positive feedback loop is maintained through estrogen-mediated stimulation of MCF-7 cell proliferation, which in turn results in greater secretion of interleukin 6 and its receptor IL-6 and IL-6sR and prostaglandin E2 PGE2. These factors increase aromatase transcription in fibroblasts which results in continued or increased synthesis of estrogens, completing the positive feedback loop that allows for maintenance and growth of the epithelial tumor cells.

Exposure to estrogen receptor agonists or aromatase inducers would be able to accelerate this process. Conversely, aromatase inhibitors and estrogen receptor antagonists would disrupt the loop and block or even reverse the ability of the tumor cells to grow Heneweer et al.

The latter interventions are commonly practiced in the treatment of estrogen-responsive breast tumors. Human placental JEG-3 and JAR choriocarcinoma cells express high levels of aromatase, but are relatively sensitive to the cytotoxic effects of chemicals and appear more prone to apoptosis, rendering them difficult to use for screening purposes Drenth et al.

HR cells, which appear less sensitive to cytotoxicity, have been used successfully as a bioassay to screen for interferences of xenobiotics with steroidogenesis Canton et al. The H and HR a subpopulation of H that forms a monolayer in culture cell lines have been characterized in detail and shown to express all the key enzymes necessary for steroidogenesis Gazdar et al. The cells have the physiological characteristics of zonally undifferentiated human fetal adrenal cells, with the ability to produce the steroid hormones of each of the three phenotypically distinct zones found in the adult adrenal cortex Gazdar et al.

Several tissue-specific promoters appear to be active in the regulation of aromatase expression in HR cells Heneweer et al. It was also found that aromatase expression could be induced by dexamethasone, phorbolmyristateacetate. Glucocorticoids and phorbol esters are stimulants of aromatase expression in breast adipose tissue via the 1.

However, 1. The HR cell line has also been used to develop a quantitative RT-PCR method for the detection of chemicals that can up- or downregulate the expression of 11 steroidogenic enzymes Hilscherova et al. These studies demonstrate the versatility of the HR cell line as a bioassay tool for the assessment of effects on steroidogenic enzymes. It should be kept in mind that alterations in gene expression do not necessarily reflect or result in alterations of catalytic activity.

Inhibition of catalytic activity which this review makes clear is an important mechanism by which chemicals interfere with steroidogenesis and endocrine function will generally not be detected in such an assay. For example, known inhibitors of aromatase activity such as ketoconazole and aminogluthetimide have no effect on CYP19 expression Hilscherova et al.

It is also difficult to interpret the importance of slight changes in gene expression caused by a chemical perturbation without the measurement of additional functional effects. A human ovarian granulosa-like tumor cell KGN bioassay has recently been used to examine the effects of chemicals on aromatase activity Ohno et al.

This bioassay is also capable of detecting inhibitors and inducers of aromatase activity, although it is not clear if the mechanisms of induction of aromatase are the same as in HR cells or comparable to normal granulosa cells. Nevertheless, KGN cells may provide a useful ovary-relevant tool for screening endocrine-disrupting chemicals. Clearly, a combination of the measurement of steroid hormone production and the analysis of steroidogenic gene expression, in combination with determination of subsequent hormone signaling events, using several endocrinologically relevant cell systems, will provide a powerful battery of tools for the assessment of interferences with the function of steroidogenic enzymes and function.

The ability of xenobiotics to disrupt steroidogenesis and the mechanisms by which these compounds interfere with the function of steroidogenic enzymes is a relatively unexplored area of endocrine toxicology. This review has shown that structurally highly divergent groups of chemicals can interfere with steroidogenesis and cause endocrine-disrupting effects.

In many cases, perturbations of certain endocrine endpoints have been observed, but their consequences are unknown. Clearly, certain chemicals such as the azole fungicides and systemically used antifungal drugs directly interfere with steroidogenesis by acting as potent inhibitors of steroidogenic enzymes and are known to cause endocrine disruption mainly via this mechanism.

Other classes of compounds such as the TCDD-like chemicals have less consistent effects on steroidogenic enzymes and hormone synthesis, although they are well known endocrine-disrupting compounds and interfere with steroidogenesis to some extent in various in vitro and in vivo systems.

Further elucidation of the interaction between the Ah receptor—mediated pathway and the steroid biosynthesis pathway is needed to understand in more detail the effects of Ah receptor agonists such as TCDD on steroidogenic enzymes. Thus, it is to be expected that for many endocrine-disrupting compounds, more than one mechanism will play a role, inevitably resulting in complex dose-response relationships for many different endocrine parameters. Increased efforts need to be made to interpret the relevance of slight endocrine perturbations in isolated in vitro systems for the situation in intact organisms.

Biologically relevant bioassays need to be developed and environmentally realistic dose ranges need to be chosen for the assessment of the toxicological hazard of various endocrine-disrupting chemicals for humans and wildlife. Potentially large tissue and species differences in the regulation of steroidogenic enzyme expression also require more consideration and fundamental investigations in endocrine toxicology research.

Several in vitro bioassays discussed in this review provide a promising basis for a set of tools for the initial screening of compounds for their potential to interfere with the function of steroidogenic enzymes in various tissues and organisms and for the study of mechanistic bases of disruption of steroidogenesis.

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Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Thomas Sanderson. E-mail: thomas. Oxford Academic. Google Scholar. Cite Citation. Permissions Icon Permissions. Abstract Various chemicals found in the human and wildlife environments have the potential to disrupt endocrine functions in exposed organisms.

Open in new tab Download slide. Google Preview. Use of alternative promoters to express the aromatase cytochrome P CYP19 gene in breast adipose tissues of cancer-free and breast cancer patients. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Search ADS. Effects of two fungicides with multiple modes of action on reproductive endocrine function in the fathead minnow Pimephales promelas.

Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction assay with the fathead minnow Pimephales promelas. Inhibition of testicular 17 alpha-hydroxylase and 17,lyase but not 3 beta-hydroxysteroid dehydrogenase-isomerase or 17 beta-hydroxysteroid oxidoreductase by ketoconazole and other imidazole drugs. Structure-activity relationships of the inhibition of human placental aromatase by imidazole drugs including ketoconazole.

Inhibition of human adrenal steroidogenic enzymes in vitro by imidazole drugs including ketoconazole. The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione. Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. Multiple mechanisms control brain aromatase activity at the genomic and non-genomic level. Cytopathological effects of estradiol on the arcuate nucleus of the female rat.

A possible mechanism for pituitary tumorigenesis. CYP19 aromatase cytochrome P gene expression in human malignant endometrial tumors. The human CYP19 aromatase P gene: Update on physiologic roles and genomic organization of promoters.

Gonadal development and growth of chickens and turkeys hatched from eggs injected with an aromatase inhibitor. Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish.

Inhibition and induction of aromatase CYP19 activity by brominated flame retardants in HR human adrenocortical carcinoma cells. Paradoxical effect of an aromatase inhibitor, CGS , on aromatase activity in guinea pig brain. Using reproductive and developmental effects data in ecological risk assessment for oviparous vertebrates exposed to contaminants. Failure of chloro-s-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro.

Role of steroidogenic factor 1 and aromatase in temperature-dependent sex determination in the red-eared slider turtle. Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: Time-dose dependence and species comparison. Colocalization of Pc17 and cytochrome b5 in androgen-synthesizing tissues of the human. Inhibition of ACTH action on cultured bovine adrenal cortical cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin through a redistribution of cholesterol.

Effects of some persistent halogenated environmental contaminants on aromatase CYP19 activity in the human choriocarcinoma cell line JEG Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: Hormonal properties, dosage, and animal strain.

Mechanism of toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD in cultured human luteinized granulosa cells. Human adrenal CYP11B1: Localization by in situ-hybridization and functional expression in cell cultures. Effects of tributyltin chloride in vitro on the hepatic microsomal monooxygenase system in the fish Stenotomus chrysops. Effects of tributyltin in vivo on hepatic cytochrome P forms in marine fish. Effects of triphenyltin and other organotins on hepatic monooxygenase system in fish.

Expression of aromatase in the ovary: Down-regulation of mRNA by the ovulatory luteinizing hormone surge. A risk assessment of atrazine use in California: Human health and ecological aspects. Toxic equivalency factors of polychlorinated dibenzo-p-dioxins in an ovulation model: Validation of the toxic equivalency concept for one aspect of endocrine disruption.

Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Factors influencing the development and time of appearance of mammary cancer in the rat in response to estrogen. Effects of environmental antiandrogens on reproductive development in experimental animals. Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat.

Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. In vitro metabolism of chlorotriazines: Characterization of simazine, atrazine and propazine metabolism using liver microsomes from rats treated with various cytochrome P inducers.

Atrazine-induced hermaphroditism at 0. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine.

Dioxin perturbs, in a dose- and time-dependent fashion, steroid secretion, and induces apoptosis of human luteinized granulosa cells. Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model. Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts. A comparison of human HR and rat R2C cell lines as in vitro screening tools for effects on aromatase.

Assessment of the effects of chemicals on the expression of ten steroidogenic genes in the HR cell line using real-time PCR.

Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: Dose-response studies. Ikeuchi, T. A novel progestogen receptor subtype in the Japanese eel, Anguilla japonica. FEBS Lett. Ishrat, T. Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases.

Jacobs, E. Developmental regulation of the distribution of aromatase- and estrogen-receptor- mRNA-expressing cells in the zebra finch brain. Jayasinghe, B. Aberrant ligand-induced activation of G protein-coupled estrogen receptor 1 GPER results in developmental malformations during vertebrate embryogenesis. Jeong, J. Functional and developmental analysis of the blood-brain barrier in zebrafish.

Jiang, C. Jorgensen, A. Identification and characterisation of an androgen receptor from zebrafish Danio rerio. Kah, O. Lessons from the zebrafish. Biol , , 29— Kallivretaki, E. The zebrafish, brain-specific, aromatase cyp19a2 is neither expressed nor distributed in a sexually dimorphic manner during sexual differentiation. Katsu, Y. Cloning, expression and functional characterization of carp, Cyprinus carpio , estrogen receptors and their differential activations by estrogens.

Kawahara, T. Cloning and expression of genomic and complementary DNAs Encoding an estrogen receptor in the medaka fish, Oryzias latipes.

Kawai, H. Three-dimensional distribution of astrocytes in zebrafish spinal cord. Glia 36, — Kazeto, Y. Molecular characterization of three forms of putative membrane-bound progestin receptors and their tissue-distribution in channel catfish, Ictalurus punctatus.

Kim, S. Sequence and expression of androgen receptor and estrogen receptor gene in the sex types of protogynous wrasse, Halichoeres trimaculatus. Kimoto, T. Neurosteroid synthesis by cytochrome pcontaining systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis. Kishi, Y. Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells.

Kizil, C. Adult neurogenesis and brain regeneration in zebrafish. Koch, S. Characterization of four lipoprotein classes in human cerebrospinal fluid. Koenig, H. Progesterone synthesis and myelin formation by Schwann cells. Science , — Krause, D. Acta Physiol. Kriegstein, A. The glial nature of embryonic and adult neural stem cells. Kuo, J. Membrane estrogen receptors stimulate intracellular calcium release and progesterone synthesis in hypothalamic astrocytes.

Kusuhara, H. Active efflux across the blood-brain barrier: role of the solute carrier family. NeuroRx 2, 73— Ladu, M. Lipoproteins in the central nervous system. Lapergue, B. High-density lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke.

Stroke 44, — Protective effect of high-density lipoprotein-based therapy in a model of embolic stroke. Stroke 41, — Lassiter, C. Genomic structure and embryonic expression of estrogen receptor beta a ERbetaa in zebrafish Danio rerio.

Gene , — Lavenex, P. The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels. Le Goascogne, C. Neurosteroids: cytochrome Pscc in rat brain. Lephart, E. A review of brain aromatase cytochrome P Brain aromatase cytochrome P messenger RNA levels and enzyme activity during prenatal and perinatal development in the rat.

Leszczynski, D. Metabolic conversion of six steroid hormones by human plasma high-density lipoprotein. Acta , 18— Li, X. Distribution of estrogen receptor-beta-like immunoreactivity in rat forebrain. Neuroendocrinology 66, 63— Li, Y. Zebrafish: a promising in vivo model for assessing the delivery of natural products, fluorescence dyes and drugs across the blood-brain barrier.

Liao, S. Association of serum estrogen level and ischemic neuroprotection in female rats. Linard, B. Estrogen receptors are expressed in a subset of tyrosine hydroxylase-positive neurons of the anterior preoptic region in the rainbow trout. Neuroendocrinology 63, — Linetti, A. Cholesterol reduction impairs exocytosis of synaptic vesicles. Cell Sci. Liu, C. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature reviews. Neurology 9, — Liu, J.

Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Liu, X. Identification of a membrane estrogen receptor in zebrafish with homology to mammalian GPER and its high expression in early germ cells of the testis.

London, S. Steroidogenic enzymes along the ventricular proliferative zone in the developing songbird brain. Widespread capacity for steroid synthesis in the avian brain and song system. Neurosteroid production in the songbird brain: a re-evaluation of core principles. Lord, L. Rapid steroid influences on visually guided sexual behavior in male goldfish.

Louissaint, A. Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34, — Lubischer, J. Autoradiographic localization of progestin-concentrating cells in the brain of the zebra finch. Ma, C. Maggioli, E. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking.

Brain Behav. Mahesh, V. Interaction between ovarian and adrenal steroids in the regulation of gonadotropin secretion. Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids 63, — Mahley, R. Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Mangiamele, L. Mani, S. Inhibition of rat sexual behavior by antisense oligonucleotides to the progesterone receptor. Manolides, L. Influence of hydrocortisone, progesterone and testosterone on dendritic growth in vitro.

Acta Otolaryngol. Estradiol stimulates progenitor cell division in the ventricular and subventricular zones of the embryonic neocortex. Heterogeneity in progenitor cell subtypes in the ventricular zone of the zebrafish adult telencephalon. Glia 58, — Mathieu, M. Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase in the brain of the African lungfish Protopterus annectens.

Matsumoto, T. Alteration in sex-specific behaviors in male mice lacking the aromatase gene. Neuroendocrinology 77, — Matsunaga, M. Mauch, D. CNS synaptogenesis promoted by glia-derived cholesterol. Mazzucco, C. Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats.

McCarthy, M. A lumpers versus splitters approach to sexual differentiation of the brain. McCullough, L. Aromatase cytochrome P and extragonadal estrogen play a role in ischemic neuroprotection.

McEwen, B. Understanding the broad influence of sex hormones and sex differences in the brain. Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain. Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes. Ciba Found Symp , , 52— discussion 66— Meffre, D. Distribution of membrane progesterone receptor alpha in the male mouse and rat brain and its regulation after traumatic brain injury.

Mellon, S. Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. Menuet, A. Distribution of aromatase mRNA and protein in the brain and pituitary of female rainbow trout: comparison with estrogen receptor alpha. Molecular characterization of three estrogen receptor forms in zebrafish: binding characteristics, transactivation properties, and tissue distributions.

Expression and estrogen-dependent regulation of the zebrafish brain aromatase gene. Mhaouty-Kodja, S. Role of the androgen receptor in the central nervous system. Micevych, P. Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures.

Synthesis and function of hypothalamic neuroprogesterone in reproduction. Estradiol regulation of progesterone synthesis in the brain. The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats. Neuroendocrinology 78, 29— Mitani, Y. Hypothalamic Kiss1 but not Kiss2 neurons are involved in estrogen feedback in medaka Oryzias latipes. Mitra, S. Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha.

Morali, G. Inhibition of testosterone-induced sexual behavior in the castrated male rat by aromatase blockers. Morini, M. Nuclear and membrane progestin receptors in the European eel: characterization and expression in vivo through spermatogenesis.

Part A Mol. Mouriec, K. Early regulation of brain aromatase cyp19a1b by estrogen receptors during zebrafish development. Synthesis of estrogens in progenitor cells of adult fish brain: evolutive novelty or exaggeration of a more general mechanism implicating estrogens in neurogenesis? Mourot, B.

Two unrelated putative membrane-bound progestin receptors, progesterone membrane receptor component 1 PGMRC1 and membrane progestin receptor mPR beta, are expressed in the rainbow trout oocyte and exhibit similar ovarian expression patterns. Mukai, H. Modulation of synaptic plasticity by brain estrogen in the hippocampus. Cloning and sequencing of the gilthead sea bream estrogen receptor cDNA.

DNA Seq. Murashov, A. Na, W. Nagler, J. The complete nuclear estrogen receptor family in the rainbow trout: discovery of the novel ERalpha2 and both ERbeta isoforms. Navas, J. Do gonadotrophin-releasing hormone neurons express estrogen receptors in the rainbow trout? A double immunohistochemical study. Nico, B. Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier.

Noctor, S. Neurons derived from radial glial cells establish radial units in neocortex. Nature , — Okada, M. Olsson, P. Molecular cloning and characterization of a nuclear androgen receptor activated by ketotestosterone. Ormerod, B. Reproductive status influences cell proliferation and cell survival in the dentate gyrus of adult female meadow voles: a possible regulatory role for estradiol.

Reproductive status influences the survival of new cells in the dentate gyrus of adult male meadow voles. Dysfunctional HDL in acute stroke. Atherosclerosis , 75— Pakdel, F. Full-length sequence and in vitro expression of rainbow trout estrogen receptor cDN.

Pang, Y. Involvement of estradiolbeta and its membrane receptor, G protein coupled receptor 30 GPR30 in regulation of oocyte maturation in zebrafish, Danio rario. Estrogen signaling characteristics of Atlantic croaker G protein-coupled receptor 30 GPR30 and evidence it is involved in maintenance of oocyte meiotic arrest. Panzica, G. Organizational effects of estrogens on brain vasotocin and sexual behavior in quail.

Pardridge, W. Transport of steroid hormones through the rat blood-brain barrier. Primary role of albumin-bound hormone. Parimisetty, A. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research.

Neuroinflammation 13, Pasmanik, M. Aromatase and 5 alpha-reductase in the teleost brain, spinal cord, and pituitary gland. Changes in brain aromatase and 5 alpha-reductase activities correlate significantly with seasonal reproductive cycles in goldfish Carassius auratus. Pawlisch, B. Pellegrini, E. Relationships between aromatase and estrogen receptors in the brain of teleost fish.

Identification of aromatase-positive radial glial cells as progenitor cells in the ventricular layer of the forebrain in zebrafish. Ball, and F. Pelletier, G. Steroidogenic enzymes in the brain: morphological aspects. Perkins, A. The ram as a model for behavioral neuroendocrinology. Petersen, S. Novel progesterone receptors: neural localization and possible functions.

Peterson, R. Radial glia express aromatase in the injured zebra finch brain. Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch Taeniopygia guttata. Aromatase is pre-synaptic and sexually dimorphic in the adult zebra finch brain. Petralia, S. In the ventral tegmental area picrotoxin blocks FGIN induced increases in sexual behavior of rats and hamsters.

Psychopharmacology , — Petrone, A. Phan, A. Low doses of 17beta-estradiol rapidly improve learning and increase hippocampal dendritic spines. Neuropsychopharmacology 37, — Pouso, P. Brain androgen receptor expression correlates with seasonal changes in the behavior of a weakly electric fish, Brachyhypopomus gauderio. Putnam, C.

Acute activation of the adrenocorticotropin-adrenal axis: effect on gonadotropin and prolactin secretion in the female rat. Quan, G. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Ravi, V. Rapidly evolving fish genomes and teleost diversity.

Roncali, L. Microscopical and ultrastructural investigations on the development of the blood-brain barrier in the chick embryo optic tectum. Acta Neuropathol. Roof, R. Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. Neurotrauma 17, — Roselli, C. Role of aromatization in anticipatory and consummatory aspects of sexual behavior in male rats.

Brain aromatase: roles in reproduction and neuroprotection. Rosner, W. Free estradiol and sex hormone-binding globulin. Steroids 99, — Rossetti, M. Oestrogens and progestagens: synthesis and action in the brain.

Rothenaigner, I. Clonal analysis by distinct viral vectors identifies bona fide neural stem cells in the adult zebrafish telencephalon and characterizes their division properties and fate. Development , — Roy, S. Characterization of membrane progestin receptor alpha mPRalpha of the medaka and role in the induction of oocyte maturation. Sabo-Attwood, T. Differential expression of largemouth bass Micropterus salmoides estrogen receptor isotypes alpha, beta, and gamma by estradiol.

Sager, T. Estrogen and environmental enrichment differentially affect neurogenesis, dendritic spine immunolabeling and synaptogenesis in the hippocampus of young and reproductively senescent female rats. Sakamoto, H. Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis. Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats.

Salbert, G. Localization of the estradiol receptor mRNA in the forebrain of the rainbow trout. Saldanha, C. Synaptocrine signaling: steroid synthesis and action at the synapse. Sar, M. Immunohistochemical localization of the androgen receptor in rat and human tissues. Sasano, H. Aromatase in the human central nervous system. Schlinger, B. The activity and expression of aromatase in songbirds. Neurosteroidogenesis: insights from studies of songbirds. Neurosteroids and brain sexual differentiation.

Schmidt, K. Neurosteroids, immunosteroids, and the Balkanization of endocrinology. Schumacher, M. Progesterone: therapeutic opportunities for neuroprotection and myelin repair. Scordalakes, E.

Oestrogen's masculine side: mediation of mating in male mice. Sellers, K. Rapid modulation of synaptogenesis and spinogenesis by 17beta-estradiol in primary cortical neurons. Seredynski, A. Estrogen receptor beta activation rapidly modulates male sexual motivation through the transactivation of metabotropic glutamate receptor 1a. Neuroestrogens rapidly regulate sexual motivation but not performance.

Shah, A. DHEA and estradiol levels in brain, gonads, adrenal glands, and plasma of developing male and female European starlings. Shahrokhi, N. Neuroprotective antioxidant effect of sex steroid hormones in traumatic brain injury. Shi, Y. G-protein-coupled estrogen receptor 1 is involved in brain development during zebrafish Danio rerio embryogenesis.

Shughrue, P. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. Si, D. Progesterone protects blood-brain barrier function and improves neurological outcome following traumatic brain injury in rats. Sinchak, K. Estrogen induces de novo progesterone synthesis in astrocytes. Slewa-Younan, S.

Sex differences in injury severity and outcome measures after traumatic brain injury. Socorro, S. Two estrogen receptors expressed in the teleost fish, Sparus aurata : cDNA cloning, characterization and tissue distribution. Sohrabji, F. Soma, K. Sperry, T. Characterization of two nuclear androgen receptors in Atlantic croaker: comparison of their biochemical properties and binding specificities.

Identification of two nuclear androgen receptors in kelp bass Paralabrax clathratus and their binding affinities for xenobiotics: comparison with Atlantic croaker Micropogonias undulatus androgen receptors. Spritzer, M. Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Stephens, S. Absent progesterone signaling in kisspeptin neurons disrupts the LH surge and impairs fertility in female mice.

Sterling, R. The distribution of nuclear progesterone receptor in the hypothalamus and forebrain of the domestic hen. Cell Tissue Res. Stewart, P. Structural and histochemical features of the avian blood-brain barrier. Stone, D. Astrocytes and microglia respond to estrogen with increased apoE mRNA in vivo and in vitro. Strobl-Mazzulla, P. Brain aromatase Cyp19A2 and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis : neuroanatomical and functional relations.

Brain aromatase from pejerrey fish Odontesthes bonariensis : cDNA cloning, tissue expression, and immunohistochemical localization. Progenitor radial cells and neurogenesis in pejerrey fish forebrain. Messenger RNAs encoding steroidogenic enzymes are expressed in rodent brain. Sugiyama, D. Characterization of the efflux transport of 17beta-estradiol-Dbeta-glucuronide from the brain across the blood-brain barrier.

Sugiyama, N. Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain. Psychiatry 14, — Suzuki, S. Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors alpha and beta. Heffner; Danny J. Schust The Reproductive System at a Glance. John Wiley and Sons. Retrieved 28 November Curr Med Chem.

Biophysical Journal. Molecular and Cellular Endocrinology. Brain Behav Evol. Acta Biochim Pol. International Journal of Molecular Sciences.

Oxytocin Vasopressin. Thyroid hormones T 3 T 4 Calcitonin Thyroid axis. Testosterone AMH Inhibin. Glucagon Insulin Amylin Somatostatin Pancreatic polypeptide. Gastrin Ghrelin. Enteroglucagon Peptide YY. Leptin Adiponectin Resistin. Endogenous steroids. Nuclear receptor modulators. Agonists: Arachidonic acid metabolites e. See here instead. Authority control NDL : Categories : Steroid hormones Steroids. Namespaces Article Talk. Views Read Edit View history.

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