Regulation of Follicle-Stimulating Hormone β and Common α-Subunit Messenger Ribonucleic Acid by Gonadotropin-Releasing Hormone and Estrogen in the Sheep Pituitary

Abstract

The effect of gonadotropin-releasing hormone (GnRH) and/or estradiol (E₂) on pituitary messenger ribonucleic acid (mRNA) levels of luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ) and the common α-subunit were determined in anterior pituitary glands from ovariectomized (OVX) ewes. Hypothalamo-pituitary disconnected (HPD) ewes receiving appropriate hormonal treatment were used to assess the relative roles of GnRH and E₂ in directly regulating FSHβ and α-subunit mRNA levels. Levels of LHβ mRNA were increased in OVX animals compared with intact controls, and E₂ treatment of OVX animals significantly reduced mRNA levels of LHβ and FSHβ. HPD substantially reduced FSHβ and α-subunit mRNA levels. Treatment of OVX/HPD animals with pulses of GnRH (250 ng/2 h) for 1 week restored FSHβ and α-subunit mRNA to OVX levels. Combined GnRH and E₂ treatment significantly lowered FSHβ mRNA levels, but resulted in a rise in α-subunit mRNA levels. Treatment of OVX/HPD ewes with E₂ alone had no effect on FSHβ and α-subunit mRNA levels. These findings indicate that E₂ acts directly on the pituitary to negatively regulate FSHβ mRNA levels, and to positively regulate α-subunit mRNA levels in the presence of GnRH.

A Nongenomic Action of Estradiol as the Mechanism Underlying the Acute Suppression of Secretion of Luteinizing Hormone in Ovariectomized Ewes1

“…This decrease in FSH secretion was first noted approximately 4 h after E 2 priming, and concentrations of FSH remained low for the next 8 h. In the intact ewes, the half-life of FSH has been reported to range from 33 to 116 min [26,39,40], and although a longer half-life for FSH has been detected in OVX ewes compared with intact ewes (90 vs. 30 min) [40], the time frame for the delayed decrease in FSH is consistent with the idea of a genomic mechanism underlying the negative feedback of E 2 on secretion of FSH. If E 2 inhibited FSH secretion via nongenomic mechanisms, then the decrease would be expected in 90 min or less rather than after 4 h. Similar negative-feedback effects of E 2 on secretion of FSH have been reported previously [4,8]. A direct effect of E 2 on secretion of FSH at the pituitary gland has been demonstrated using OVX/HPD ewes maintained with GnRH pulses [4,8,10] and in cultured ovine pituitary cells [6,7].…”

“…If E 2 inhibited FSH secretion via nongenomic mechanisms, then the decrease would be expected in 90 min or less rather than after 4 h. Similar negative-feedback effects of E 2 on secretion of FSH have been reported previously [4,8]. A direct effect of E 2 on secretion of FSH at the pituitary gland has been demonstrated using OVX/HPD ewes maintained with GnRH pulses [4,8,10] and in cultured ovine pituitary cells [6,7]. In both in vivo and in vitro paradigms, the decrease in secretion of FSH was accompanied by a decrease in levels of FSHb mRNA in the pituitary gland [4,8,10,12,13].…”

“…Additionally, E 2 is capable of decreasing the secretion of FSH several hours after its administration [4][5][6][7][8]. Traditionally, the mechanism by which E 2 exerts its effects has been thought to occur exclusively through regulation of the transcription of target genes.…”

Effects of intracerebroventricular infusion of genistein on gonadotrophin subunit mRNA and immunoreactivity of gonadotrophins and oestrogen receptor-α in the pituitary cells of the anoestrous ewe

“…This is not in agreement with the observations of a direct inhibitory action of oestradiol on the transcription of FSHsubunits genes in the sheep pituitary (McNeilly, 1988;Mercer et al, 1989). The different response of LH and FSH cells on the genistein infusion can be due to the different reproductive season investigated and/or the different mechanisms of LH and FSH synthesis and storage.…”

Regulation of gonadotropin subunit gene transcription

“…Colin et al (1996) reported that E 2 suppressed basal activity of a human -promoter-LUC construct in the pituitaries of OVX transgenic mice, but enhanced GnRH responsiveness. We and others have also observed that E 2 potentiates GnRH stimulation of gene expression, but it is unknown whether the effect is direct or indirect (that is, increasing GnRH receptor numbers) (Mercer et al 1989, Dalkin et al 1990, Kerrigan et al 1993, Turgeon et al 1996, Kawakami & Winters 1999.…”