Estrogen Regulation of Follicle Stimulating Hormone in Cell Cultures of Sheep Pituitaries¹,²

Abstract

Cell cultures of ovine pituitaries were maintained for up to 3 weeks. A specific double antibody radioimmunoassay was used to measure FSH in the media and cells. The rate of FSH synthesis increased in the cultures during the first 4-6 days to a level of approximately 50 ng/day/106 cells, generally remained constant for 2 weeks and then decreased. The FSH produced in vitro migrated similarly to highly purified ovine FSH on P-60 polyacrylamide gel filtration columns and had a biological potency essentially identical to that of the highly purified FSH standard. Addition of 17beta-estradiol (E2) at 10-9M on days 2 or 6 incubation decreased FSH synthesis greater than 95% within 30 h. Time-course analysis revealed that the effect of E2 can be observed as early as 6 h after treatment. FSH synthesis resumed after removal of E2 and reached control levels within 6 days. The lowest effective dose of E2 was 10-11M; E2 at 5 X 10-11M maintained FSH production at approximately 50% of the control levels. Diethylstilbestrol was as active estriol was 1/10th as active and 17alpha-estradiol was 1/100th as active as E2. Progesterone (P), 5alpha-pregnane-3,20-dione (5alphaDHP), 20alpha-hydroxy-pregn-4-en-3-one(20alpha-OHP), testosterone, 5alpha-dihydrotestosterone and corticosterone had no effect on FSH levels. These findings suggest that estrogen is capable of playing a major role in FSH synthesis and release by action directly at the pituitary level.

Differential effects of LH-RH immunoneutralization on LH and FSH secretion in the ewe

“…Androgens do not seem to be of primary importance (Dobson & Ward, 1977) and oestradiol has been implicated as the most likely candidate by Radford, Nancarrow & Findlay (1978), who also observed maintenance of plasma FSH concentrations with suppressed LH levels after administration of an anaesthetic to ewes during the late follicular phase. In ovariectomized ewes administration of oestradiol suppressed FSH concentrations (Goodman, Pickover & Karsch, 1981), although these authors proposed that another factor, possibly "inhibin" (Cummins, O'Shea, Bindon, Lee & Findlay, 1983) (Miller, Knight, Grimek & Gorski, 1977). Also, in ovariectomized ewes actively immunized against LH-RH and with suppressed plasma levels of FSH, these values were reduced even further by administration of oestradiol benzoate (Fraser et ai, 1981).…”

Dynamic regulation of pituitary mRNAs for bone morphogenetic protein (BMP) 4, BMP receptors, and activin/inhibin subunits in the ewe during the estrous cycle and in cultured pituitary cells

“…In contrast, chronic GnRH did not modify the amount of mRNA for BMP4, BMP receptors, and Id2. Concerning the effect of the treatment with E 2 for 48 h, it inhibits the FSHb mRNA and FSH release (data not shown) as expected (Miller et al 1977, Baratta et al 2001. However, E 2 does not affect the expression of the mRNA for BMPR1A (ALK3) and BMPR2, but tends to increase that of BMPR1B (ALK6) mRNA.…”

Effect of phytoestrogens on basal and GnRH-induced gonadotropin secretion

“…This has been demonstrated in several species using both in vivo and in vitro models (Lindzey et al 2006, Arreguin-Arevalo et al 2007. Groups using ovine pituitary cells in culture have clearly demonstrated that treatment with E 2 attenuates FSH secretion and intracellular synthesis (Miller et al 1977, Huang & Miller 1980, Nett et al 2002. In particular, E 2 suppresses these parameters by decreasing FSHb expression (Miller & Miller 1996, Baratta et al 2001.…”