Distinct Regulation by Steroids of Messenger RNAs for FSHR and CYP19A1 in Bovine Granulosa Cells

• Published in: Biology of reproduction Vol. 75; no. 2; pp. 217 - 225
• Main Authors: Luo, Wenxiang, Wiltbank, Milo C
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-08-2006
• Subjects: Analysis of Variance; androgen receptor; Anilides - pharmacology; Animals; Aromatase - genetics; Aromatase - metabolism; Biological and medical sciences; Cattle; Cells, Cultured; Colforsin - pharmacology; Contents; Cyclic AMP-Dependent Protein Kinases - metabolism; Dihydrotestosterone - metabolism; Dihydrotestosterone - pharmacology; Dose-Response Relationship, Drug; estradiol; Estradiol - analogs & derivatives; Estradiol - metabolism; Estradiol - pharmacology; estradiol receptor; Estrogen Antagonists - pharmacology; Female; Follicle Stimulating Hormone - metabolism; follicle-stimulating hormone receptor; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; granulosa cells; Granulosa Cells - physiology; Mammalian female genital system; Morphology. Physiology; Nitriles; Receptors, Androgen - metabolism; Receptors, FSH - genetics; Receptors, FSH - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Steroids - metabolism; Steroids - pharmacology; Testosterone - metabolism; Testosterone - pharmacology; Tosyl Compounds; Vertebrates: reproduction; Steroid; follicle- stimulating hormone receptor; estradiol receptor; Estrogen; 17β-Estradiol; Ox; granulosa cells; Ovarian hormone; Ovary; Vertebrata; Reproduction; Mammalia; Messenger RNA; Animal; Female genital system; Androgen receptor; Artiodactyla; Granulosa; Sex steroid hormone; FSH receptor; Ovarian follicle; Ungulata; Biological receptor; estradiol
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.105.047407

Steroidal regulation of gene expression in follicular cells is not completely defined. Granulosa cells from 5 mm bovine follicles were cultured and treated and steady-state mRNA levels determined for FSHR (follicle-stimulating hormone receptor) and CYP19A1 (aromatase). Cells were treated for 5 days with (0.1–300 ng/ml) 17beta-estradiol (E2), testosterone (T), or 5alpha-dihydrotestosterone (DHT). FSHR mRNA was increased by T and DHT but not E2. In contrast, CYP19A1 mRNA was induced by all doses of E2 but only high doses of T and DHT. Similarly, varying treatment duration (1–5 days) showed that FSHR was increased by T and DHT and CYP19A1 mRNA increased by E2 and T at all times. Synergism between steroid hormones and FSH or forskolin was also evaluated. FSH or E2 did not alter FSHR mRNA and did not enhance DHT stimulation of FSHR mRNA. In contrast, DHT alone had no effect on CYP19A1 mRNA but synergized with FSH plus E2 to increase CYP19A1 mRNA, probably due to induction of FSHR by DHT. Effects of E2 and T on CYP19A1 were blocked by ICI 182,780, indicating mediation by estrogen receptors. However, the specific androgen receptor antagonist bicalutamide did not block E2 or T effects on CYP19A1 but did block T and DHT stimulation of FSHR. Thus, FSHR is specifically regulated through androgen receptor, whereas CYP19A1 is regulated by multiple pathways, including estrogen receptors and cAMP/protein kinase A induced by FSHR activation in granulosa cells. These inter- and intracellular regulatory mechanisms may be critical for normal follicle growth and dominant follicle selection.