ACTH treatment disrupts ovarian IGF-I and steroid hormone production

Hyper-adrenal activity and increased glucocorticoid hormone release are ass ociated with disruptions in reproductive function and adverse effects on th e ovary. The aim of this investigation was to determine whether elevated gl ucocorticoid hormone levels can influence ovarian IGF-I synthesis and actio n in vivo. To elevate endogenous glucocorticoid levels, gilts were treated with ACTH during the luteal phase of the oestrous cycle (days 9-13) while t he control group received saline. The gilts were subsequently ovariectomize d on either day 14 or day 18 of the oestrous cycle. Follicular fluid (FF) w as collected from individual follicles; IGF-I and steroid hormone concentra tions were determined by radioimmunoassay, and IGF-binding protein (IGFBP) expression was assessed by Western ligand blotting. Granulosa cells were al so recovered and placed in culture to determine IGF-I, progesterone (P-4) a nd oestradid-17 beta (E-2) production levels. The cells were cultured in se rum-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 sits was characterized by elevated (P<0.05) cortisol l evels on day 14 and lower (P<0.05) E-2 values on both day 14 and day 18. Lo wer (P<0.05) IGF-I concentrations were also measured in the FF of ACTH-trea ted gilts collected on day 18. This altered hormone profile in FF was assoc iated with impaired IGF-I and steroid hormone synthesis by granulosa cells. IGF-stimulated P-4 production (P<0.01) by cells recovered from ACTH-treate d gilts on day 14 was lower (P<0.05). By day 18, IGF-I, P-4 and E-2 product ion by cells from the ACTH group were all significantly (P<0.05) lower. The se results demonstrate that increased glucocorticoid concentrations can dis rupt subsequent ovarian IGF-I synthesis and IGF action in vivo and can, pot entially, impair follicle maturation.