Immunoreactive corticotropin-releasing hormone and its binding sites in the rat ovary.

Abstract

Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary AC17H secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific radioimmunoassay, we measured IrCRH in extracts of rat ovaries (0.0424.126 pmol/g wet tissue). The mobility of the ovarian IrCRH molecule was similar to that of rat/human CRH by reverse phase HPLC. To investigate the CRH action in the ovary, we identified, characterized, and localized CRH receptors in the rat ovary. Binding was linear with increasing tissue concentration, saturable, and of high affinity. Scatchard analysis of '251-Tyr-ovine CRH competitive displacement curves indicated a high affinity binding site with a Kd of 6 nM and a B. value of 61 fM/mg protein. Autoradio-graphic studies revealed CRH receptors primarily in ovarian theca and stroma. We conclude that IrCRH and CRH receptors are present in rat ovaries, suggesting that this neuropeptide may play a regulatory role in this gonad, perhaps through its proinflammatory properties and/or by participating in the auto/paracrine regulation of steroid biosynthesis. Functional studies are necessary to define the role(s) of CRH in the ovary. (J. Clin. Invest. 1993. 92:961-968.)

Corticotrophin-releasing hormone inhibits insulin-like growth factor-I release from primary cultures of rat granulosa cells

“…Immunoreactive CRH and CRH receptors have been found in rat ovaries (Mastorakos et al 1993). Ovarian CRH is produced locally since both mouse and human ovarian tissue express CRH mRNA (Muglia et al 1994, Asakura et al 1997.…”

“…More recent findings have shown that CRH is also produced by the ovary where it is localised in theca cells surrounding follicles, stroma cells, mature oocytes within antral follicles and ovarian resident macrophages. In the developing corpora lutea, it is detectable in the cytoplasm of both small theca-derived and large granulosa-derived luteinized cells (Mastorakos et al 1993, Muglia et al 1994, Asakura et al 1997. It has been shown to restrain the production of oestrogen by rat and human granulosa cells (Calogero et al 1996, Ghizzoni et al 1997.…”

Possible Actions of Corticotropin-Releasing Hormone in Regulating Porcine Corpus Luteum Function

“…In addition, higher levels of immunoreactive CRH have been found in the regressing CL compared with the developing CL in humans [15], suggesting that CRH plays a role at this stage. However, the CRH concentrations in the CLs of monkeys [24], humans [14] and rats [13] have been demonstrated to increase in the developing luteal stage and to decrease in the regressing stage. Further study is needed to clarify the CRH production profile and the concrete roles of CRH in the porcine CL at the time of luteolysis.…”

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

“…Corticotropin-releasing hormone mRNA and peptide have been detected in both human and rat normal ovaries. More specifically, immunoreactive CRH (irCRH) and its binding sites have been localised in thecal and stromal cells of rat and human ovaries and in human follicular fluid (Mastorakos et al, 1993(Mastorakos et al, , 1994. Type 1 (CRHR1) and type 2 (CRHR2) CRH receptor mRNAs have also been detected in corpus luteum (Muramatsu et al, 2001).…”