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Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope.
Mol Endocrinol. 2006 Sep; 20(9):2062-79.ME

Abstract

FSH is produced by the pituitary gonadotrope to regulate gametogenesis. Steroid hormones, including androgens, progestins, and glucocorticoids, have all been shown to stimulate expression of the FSHbeta subunit in primary pituitary cells and rodent models. Understanding the molecular mechanisms of steroid induction of FSHbeta has been difficult due to the heterogeneity of the anterior pituitary. Immortalized LbetaT2 cells are a model of a mature gonadotrope cell and express the endogenous steroid receptor for each of the three hormones. Transient transfection of each receptor, along with ligand treatment, stimulates the mouse FSHbeta promoter, but induction is severely diminished using receptors that lack the ability to bind DNA, indicating that induction is likely through direct DNA binding. All three steroid hormones act within the first 500 bp of the FSHbeta promoter where six putative hormone response elements exist. The -381 site is critical for FSHbeta induction by all three steroid hormones, whereas the -197 and -139 sites contribute to maximal induction. Interestingly, the -273 and -230 sites are also necessary for androgen and progestin induction of FSHbeta, but not for glucocorticoid induction. Additionally, we find that all three receptors bind the endogenous FSHbeta promoter, in vivo, and specifically bind the -381 site in vitro, suggesting that the binding of the receptors to this element is critical for the induction of FSHbeta by these 3-keto steroid hormones. Our data indicate that androgens, glucocorticoids, and progestins act via their receptors to directly activate FSHbeta gene expression in the pituitary gonadotrope.

Authors+Show Affiliations

Department of Reproductive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0674, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16675544

Citation

Thackray, Varykina G., et al. "Androgens, Progestins, and Glucocorticoids Induce Follicle-stimulating Hormone Beta-subunit Gene Expression at the Level of the Gonadotrope." Molecular Endocrinology (Baltimore, Md.), vol. 20, no. 9, 2006, pp. 2062-79.
Thackray VG, McGillivray SM, Mellon PL. Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. Mol Endocrinol. 2006;20(9):2062-79.
Thackray, V. G., McGillivray, S. M., & Mellon, P. L. (2006). Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. Molecular Endocrinology (Baltimore, Md.), 20(9), 2062-79.
Thackray VG, McGillivray SM, Mellon PL. Androgens, Progestins, and Glucocorticoids Induce Follicle-stimulating Hormone Beta-subunit Gene Expression at the Level of the Gonadotrope. Mol Endocrinol. 2006;20(9):2062-79. PubMed PMID: 16675544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. AU - Thackray,Varykina G, AU - McGillivray,Shauna M, AU - Mellon,Pamela L, Y1 - 2006/05/04/ PY - 2006/5/6/pubmed PY - 2006/9/29/medline PY - 2006/5/6/entrez SP - 2062 EP - 79 JF - Molecular endocrinology (Baltimore, Md.) JO - Mol Endocrinol VL - 20 IS - 9 N2 - FSH is produced by the pituitary gonadotrope to regulate gametogenesis. Steroid hormones, including androgens, progestins, and glucocorticoids, have all been shown to stimulate expression of the FSHbeta subunit in primary pituitary cells and rodent models. Understanding the molecular mechanisms of steroid induction of FSHbeta has been difficult due to the heterogeneity of the anterior pituitary. Immortalized LbetaT2 cells are a model of a mature gonadotrope cell and express the endogenous steroid receptor for each of the three hormones. Transient transfection of each receptor, along with ligand treatment, stimulates the mouse FSHbeta promoter, but induction is severely diminished using receptors that lack the ability to bind DNA, indicating that induction is likely through direct DNA binding. All three steroid hormones act within the first 500 bp of the FSHbeta promoter where six putative hormone response elements exist. The -381 site is critical for FSHbeta induction by all three steroid hormones, whereas the -197 and -139 sites contribute to maximal induction. Interestingly, the -273 and -230 sites are also necessary for androgen and progestin induction of FSHbeta, but not for glucocorticoid induction. Additionally, we find that all three receptors bind the endogenous FSHbeta promoter, in vivo, and specifically bind the -381 site in vitro, suggesting that the binding of the receptors to this element is critical for the induction of FSHbeta by these 3-keto steroid hormones. Our data indicate that androgens, glucocorticoids, and progestins act via their receptors to directly activate FSHbeta gene expression in the pituitary gonadotrope. SN - 0888-8809 UR - https://www.unboundmedicine.com/medline/citation/16675544/Androgens_progestins_and_glucocorticoids_induce_follicle_stimulating_hormone_beta_subunit_gene_expression_at_the_level_of_the_gonadotrope_ L2 - https://academic.oup.com/mend/article-lookup/doi/10.1210/me.2005-0316 DB - PRIME DP - Unbound Medicine ER -