Hormonal regulation of gonadotropin releasing hormone receptor expression in the ewe

Abstract

Endocrine regulation of expression of GnRH receptors is an important step in the control of reproduction. During the early follicular phase of the estrous cycle in the ewe, GnRH receptor expression increases in preparation for the preovulatory surge of LH. The studies described herein were designed to further elucidate the hormonal interactions controlling GnRH receptor expression. In long-term ovariectomized ewes, neither removal of progesterone, nor the presence of estradiol affected the expression of GnRH receptors. However, in ewes ovariectomized during the luteal phase of the estrous cycle and immediately implanted with progesterone and estradiol for 48 hours, low levels of estradiol for 24 hours were required to increase GnRH receptor mRNA following the removal of progesterone. In ovariectomized ewes following hypothalamic-pituitary disconnection, low levels of estradiol and pulsatile GnRH were required to increase GnRH receptor expression within 24 hours of treatment initiation. These results suggest an interaction between estradiol and GnRH is involved in increasing GnRH receptor expression during the periovulatory period. How progesterone, estradiol and, GnRH interact to increase GnRH receptors is unknown, but a possible candidate involved in mediating these interactions may be the cell specific transcription factor, steroidogenic factor-1 (SF-1). SF-1 mRNA increased within 24 hours of treatment of ewes with prostaglandin F₂(α) compared to ewes in the luteal phase of the estrous cycle. This suggests that progesterone may have an inhibitory effect on SF-1 mRNA. SF-1 mRNA was similar between ovariectomized ewes and ovariectomized ewes following hypothalamic-pituitary disconnection treated with estradiol and GnRH. Treatment with estradiol or GnRH alone did not increase SF-1 mRNA. The results of these experiments suggest that progesterone removal as well as the presence of estradiol and GnRH are required to increase GnRH receptor expression during the early follicular phase in the ewe. Further, the transcription factor, SF-1 may be involved in mediating the effects of these hormones on GnRH receptor expression.