Estradiol Modulation of GNRH-Stimulated LH Release in Rat Anterior Pituitary Cells: Involvement of Dihydropyridine-Sensitive Calcium Channels

Abstract

Although enhancement of GnRH-stimulated luteinizing hormone (LH) release by estradiol (E2) has been established, it is not known at what stages of the process of transduction E₂ acts. We investigated the release of LH in response to GnRH and to Bay K 8644, an activator of L-type calcium channels, in a culture of pituitary cells obtained from ovariectomized females, these cells having being treated or not with E₂ (OVX + E₂ and OVX). We studied the effects of D600, an antagonist of T- and L-type calcium channels, and PN 200-110, an antagonist of L-type calcium channels. The effects of the latter were studied in protein kinase C-depleted cells in order to investigate the possible phosphorylation of these channels. D600 caused a decrease in GnRH-stimulated LH release in OVX and OVX + E₂ cells. However, this decrease was greater in OVX + E₂ cells, suggesting that at least one type of calcium channels may be involved as a result of treatment with E₂. We confirmed the involvement of L-type calcium channels in the action of GnRH since the GnRH-stimulated LH release was enhanced in the presence of Bay K 8644 in OVX cells. Bay K 8644 alone increased basal LH in a dose-dependent manner only in OVX + E₂ cells. PN 200-110 induced a decrease of GnRH-stimulated LH release only in OVX + E₂ cells. These results suggest that L-type calcium channels are activated in E₂-treated cells. The dose-dependent decrease cused by PN 200-110 in OVX + E₂ cells disappeared in the OVX + E₂ PKC-depleted cells. This result was confirmed with Bay K 8644 and suggests a phosphorylation of dihydropyridine-sensitive calcium channels by protein kinase C.

A Transient Effect of Estrogen on Calcium Currents and Electrophysiological Responses to Gonadotropin-Releasing Hormone in Ovine Gonadotropes

“…E2 modifies Ca2+ entry in other reproductive tis sues [22] and clonal pituitary cells [23]. It has been sug gested that without E2, L-type Ca2+ channels may not par ticipate in GnRH-stimulated LH release [24], In the present paper we have used patch-clamp recording to determine directly whether or not exposure to E2 can change Ca2+ currents in gonadotropes obtained from anoestrous ewes and maintained in short-term culture.…”

Pituitary adenylate cyclase-activating polypeptide induces expression of corticosteroid-binding globulin in cultured fetal hepatocytes: synergy with tri-iodothyronine

“…This type of interaction between hormone effects triggered at the level of nuclear receptors and that of cell membrane receptors has been observed before. In pituitary cells, for example, glucocorticoids and oestrogens modulate the gene expression of pro-opiomelanocortin and luteinizing hormone responses to gonadotropin-releasing hormone respectively [31,32]. Also, oestrogens have been shown to up-regulate thyrotropin-releasing hormone receptors in the pituitary [33].…”