Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries.

Abstract

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutea. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutea and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may be related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively.

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.…”

“…Each pig was euthanized by electric shock as is usually done in local abattoirs. The luteal stage was classified as early (days 3-5 after ovulation), mid (days 8-11), late (days [14][15][16] or regressed (days [19][20][21] by macroscopic observation of the ovaries [1] and confirmed by measuring P concentrations in CLs (n=4/each stage). For gene expression studies, the CLs were immediately separated from the ovaries, frozen rapidly in liquid nitrogen and stored at -80C until use.…”

“…CRH and CRH-R have been identified in the human placenta [8,17], endometrium [11,12] and ovaries [3,14]. In monkeys, the genes and proteins for CRH and CRH-R are expressed in the CL during the menstrual cycle [24].…”

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).…”

Follicular Fluid Cortisol Releasing Hormone (CRH) Levels and Assisted Reproductive Treatment (ART) Outcomes

“…CRH gene expression has been found to be predominantly abundant in primary antral follicles and mature human ovarian follicles, implicating an autocrine role for ovarian CRH in follicular maturation [8], ovulation, luteolysis and oocyte maturation processes [9] [10]. CRH peptide has also been detected in the cytoplasm of theca and stromal cells of ovarian follicles at all stages of development, as well as in the corpora lutea of both human and rat ovaries.…”