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 (P4) and oestradiol-17β (E2) 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 (A4), or (d) IGF-I with FSH and A4. The FF from ACTH-treated gilts was characterized by elevated (P<0.05) cortisol levels on day 14 and lower (P<0.05) E2 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. IGF-stimulated P4 production (P<0.01) by cells recovered from ACTH- treated gilts on day 14 was lower (P<0.05). By day 18, IGF-I, P4 and E2 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.