ACTH treatment disrupts ovarian IGF-I and steroid hormone production

Abstract

Hyper-adrenal activity and increased glucocorticoid hormone release are associated with disruptions in reproductive function and adverse effects on the ovary. The aim of this investigation was to determine whether elevated glucocorticoid hormone levels can influence ovarian IGF-I synthesis and action in vivo. To elevate endogenous glucocorticoid levels, gilts were treated with ACTH during the luteal phase of the oestrous cycle (days 9-13) while the control group received saline. The gilts were subsequently ovariectomized on either day 14 or day 18 of the oestrous cycle. Follicular fluid (FF) was collected from individual follicles; IGF-I and steroid hormone concentrations were determined by radioimmunoassay, and IGF-binding protein (IGFBP) expression was assessed by Western ligand blotting. Granulosa cells were also recovered and placed in culture to determine IGF-I, progesterone (P 4 ) and oestradiol-17 (E 2 ) production levels. The cells were cultured in serum-free medium for 5 days and supplemented with: (a) media alone, (b) IGF-I, (c) FSH and androstenedione (A 4 ), or (d) IGF-I with FSH and A 4 . The FF from ACTH-treated gilts was characterized by elevated (P<0·05) cortisol levels on day 14 and lower (P<0·05) E 2 values on both day 14 and day 18. Lower (P<0·05) IGF-I concentrations were also measured in the FF of ACTH-treated gilts collected on day 18. This altered hormone profile in FF was associated with impaired IGF-I and steroid hormone synthesis by granulosa cells. IGFstimulated P 4 production (P<0·01) by cells recovered from ACTH-treated gilts on day 14 was lower (P<0·05). By day 18, IGF-I, P 4 and E 2 production by cells from the ACTH group were all significantly (P<0·05) lower. These results demonstrate that increased glucocorticoid concentrations can disrupt subsequent ovarian IGF-I synthesis and IGF action in vivo and can, potentially, impair follicle maturation.

Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex

“…ACTH stimulates the conversion of cholesterol to pregnenolone in the adrenal cortex (Simpson and Waterman, 1988), which is rapidly converted to progesterone, 17αhydroxyprogesterone and androstenedione by the enzymes 3β-HSD and 17α-hydroxylase/17,20-lyase (cytochrome P450c17) respectively. Although long-term administration of ACTH seems to disrupt ovarian steroidogenesis (Viveiros and Liptrap, 2000), the short-term administration used in this study may not have affected any of the ovarian functions.…”

Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system

“…Using cultures of rat osteoblasts, Delany and Canalis 44 demonstrated that cortisol decreased Igf1 mRNA by approximately 50% through decreasing gene transcription. Furthermore, studies in the pig have shown that increased glucorticoid concentrations can disrupt ovarian IGF1 synthesis and IGF action both in vitro 45 and in vivo 46 . In rats, both acute and chronic corticosterone administration significantly decreased Bdnf mRNA and protein in the hippocampus 47 48 .…”

Restraint Stress Impairs Oocyte Developmental Potential in Mice: Role of CRH-Induced Apoptosis of Ovarian Cells1

“…Glucocorticoids were found to enhance FSH-stimulated progesterone synthesis in cultured granulosa cells of rats and cattle [77][78][79] and to suppress P450 aromatase activity and decrease the number of LH receptors in rats [78,80], cattle [79], and pigs [81]. Furthermore, porcine studies have demonstrated that increased glucocorticoid concentrations can disrupt ovarian IGF1 synthesis and IGF action both in vitro and in vivo [82,83]. On the other hand, glucocorticoids were found to promote androgen production by cultured thecal cells in cattle [84].…”