Comparative effects of androgens and catecholestrogens on progesterone production by porcine granulosa cells.
The objective of the present studies was to evaluate and compare the effects of 5 alpha-dihydrotestosterone (DHT) to those of 2-hydroxyestradiol (2-OH-E2) and 2-methoxyestradiol (2-MeO-E2) on progesterone production in cultured porcine granulosa cells. Granulosa cells were exposed to various treatments of DHT, 2-OH-E2 and 2-MeO-E2 in the absence or presence of follicle stimulating hormone (FSH) for 4 days and concentrations of progesterone in medium and cell numbers were determined. In the absence of FSH, maximally effective concentrations of DHT (1 micrograms/ml) and 2-OH-E2 (4 micrograms/ml) stimulated progesterone production (ng/10(5) cells/48 h) to 2.2 +/- 0.2- and 10.8 +/- 2.2-fold of controls (n = 4 experiments), respectively. In the presence of 200 ng/ml FSH, progesterone production stimulated by 1 micrograms/ml DHT and 4 micrograms/ml 2-OH-E2 was 5.4 +/- 1.1- and 15.5 +/- 6.0-fold of controls (n = 4 experiments), respectively. Thus, FSH appeared to enhance the response of both DHT and 2-OH-E2. The dose-response of DHT was biphasic in the presence and absence of FSH, such that progesterone production in the presence of 8 micrograms/ml DHT was similar to basal progesterone production. Concurrent treatment with saturating concentrations of 2-OH-E2 and DHT resulted in fully additive increases in progesterone production. Testosterone mimicked the effect of DHT. In comparison, concurrent treatment of saturating concentrations of 2-MeO-E2 and DHT or 2-MeO-E2 and 2-OH-E2 resulted in progesterone production that was only partially additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Spicer
L J
LJ
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Hammond
J M
JM
D000077584:2-Methoxyestradiol; D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D010063:Ovum / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis* / Q000494:pharmacology; D013552:Swine; D013739:Testosterone / Q000494:pharmacology
D002393:Estrogens, Catechol; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D000077584:2-Methoxyestradiol; D005485:Flutamide; D005640:Follicle Stimulating Hormone; C001390:2-hydroxyestradiol; C002828:19-norandrostenedione