Hormonal Regulation of GnRH and LHβ mRNA Expression in Cultured Rat Granulosa Cells

Abstract

We have recently demonstrated that the rat ovary expresses LHbeta, FSHbeta, and the common alpha subunit mRNA. In the present report, we studied the regulation of LHbeta and of gonadotropin-releasing hormone (GnRH) mRNA expression in granulosa cells that were isolated from immature rats treated with either estrogen or pregnant mare serum gonadotropin (PMSG). In both cell types, GnRH agonist treatment resulted in a decrease in LHbeta mRNA expression. However, only in cells derived from PMSG-treated rats, GnRH treatment produced an increase in GnRH mRNA expression. A markedly increased GnRH mRNA expression was also obtained in granulosa cells derived from PMSG-primed rats in response to LH. In addition, FSH reduced the expression of LHbeta mRNA in granulosa cells from estrogen-primed rats. These results suggest that the expression of LHbeta in the ovary is regulated by locally produced GnRH and by FSH from either the ovary or the pituitary.

Functional Exploration of the Adult Ovarian Granulosa Cell Tumor-Associated Somatic FOXL2 Mutation p.Cys134Trp (c.402C>G)

“…It has been shown that this sequence is bound by a Smad3-Foxl2 heterodimer [29]. Though it is best known and studied in the pituitary, recent evidence suggests that the GnRH/GnRHR system is present in the ovary [30], [31]. However, the physiological implications of this are still unclear.…”

Noradrenaline modulates the presence of gonadotropin-releasing hormone in ovary. The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus II in rat.

“…However, we might assume that the presence of intraovarian GnRH causes LH release in the ovary (data not shown), as stated by Schirsman-Hildesheim et al [43]. These authors demonstrated that the ovarian LH might be synthesized in a heterologous/homologous way [43,44]. Therefore, these findings might imply the existence of a local GnRH-gonadotropin axis in the mammals ovary that might be involved in the processes leading to the continuity of the oestrous cycle, and might be responsible for the P 4 increase in the ovary incubation.…”

Intraovarian expression of GnRH-1 and gonadotropin mRNA and protein levels in Siberian hamsters during the estrus cycle and photoperiod induced regression/recrudescence

“…Because estrogen treatment decreases GnRH-1 mRNA levels in human luteal granulosa cells, a result reversed by estrogen antagonists [22], the observed SD increase in GnRH-1 mRNA in the present study (Figure 3) could be due to significantly lower estrogen levels, and lower GnRH-1 levels in the PT group may then be related to newly resumed estrogen production (Figures 2, 3). This is further strengthened by immunolocalization of GnRH protein in granulosa, especially luteal granulosa cells in hamsters, primates, and rats (Figure 4) [6, 16]. …”

“…Regulation of intraovarian gonadotropins is not fully understood; control may be local, by the hypothalamus, or the pituitary, or a combination of regulatory factors may act in concert. Indeed, ovarian GnRH, and ovarian or pituitary FSH can regulate ovarian LHβ mRNA expression in isolated rat granulosa cells [16]. The additional intraovarian spike of both gonadotropins during diestrus (Figure 2B, 2C) mirrors the peak in GnRH (Figure 2A), a pattern that does not mimic pituitary mRNA, but does suggest differential regulation in the ovary and the pituitary.…”

“…Regulation of the ovarian GnRH - gonadotropin axis is also not fully understood. Down regulation of GnRH mRNA levels in the ovary by estrogen, gonadotropins, and melatonin has been suggested (see reviews; 15, 20, 26], and, recently it has been shown that ovarian GnRH and pituitary or ovarian FSH, may regulate LH levels in rat ovaries [16]. …”