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

• Published in: Journal of endocrinology Vol. 174; no. 3; pp. 493 - 498
• Main Authors: Calogero, AE, Barreca, A, Burrello, N, Palermo, I, Giordano, G, D'Agata, R, Vicari, E
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01-09-2002; Portland Press
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Corticotropin-Releasing Hormone - pharmacology; Dose-Response Relationship, Drug; Estrogens - metabolism; Female; Fundamental and applied biological sciences. Psychology; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Hormone metabolism and regulation; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Mammalian female genital system; Rats; Rats, Sprague-Dawley; Stimulation, Chemical; Vertebrates: reproduction; Rat; Rodentia; Corticotropin releasing factor; Stress; Hypothalamic hormone; Ovary; Vertebrata; Insulin like growth factor; Mammalia; Female genital system; Steroidogenesis; Granulosa; Inhibition; Hormone releasing factor; Mechanism of action; Ovarian follicle
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1740493

Corticotrophin-releasing hormone (CRH), a neuropeptide which modulates gonadal function during stress, is expressed by several cell types of the rat ovary and is able to suppress oestrogen release from rat granulosa cells. The mechanism of this effect is, however, not known. Since insulin-like growth factor (IGF)-I is produced by rat granulosa cells and exerts a synergistic role with FSH on granulosa cell steroidogenesis, we hypothesised that CRH may suppress oestrogen release from granulosa cells by inhibiting IGF-I release and/or stimulating the release of its binding protein (IGFBP-3). To test this hypothesis, granulosa cells were obtained from immature female Sprague-Dawley rats primed with diethylstilboestrol, and hormone concentrations were measured in the conditioned medium by radioimmunoassay. CRH suppressed oestrogen and IGF-I release stimulated by FSH used at a concentration of 1 IU/l, whereas it did not have any statistically significant effect on oestrogen and IGF-I release in basal conditions or in response to 5 IU/l FSH. The suppressive effects of CRH on oestrogen and IGF-I release were antagonised by a selective CRH receptor antagonist. CRH had no effects on IGFBP-3 release. CRH did not have any effect on oestrogen release stimulated by increasing concentrations of IGF-I and its suppressive effect on FSH-stimulated oestrogen release was overcome by the addition of low doses of exogenous IGF-I. In conclusion, CRH suppressed the release of oestrogen and IGF-I, but not of IGFBP-3. Thus, the inhibitory effects of CRH on oestrogen release could be mediated, partly, by a suppression of the autocrine/paracrine action of IGF-I.