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Effects of lipopolysaccharide and cyclosporin on the endocrine control of ovarian function

The effects of stimulating the immune system with lipopolysaccharide (LPS) or suppressing the immune system with cyclosporin (CS) on reproductive functions in the female rat were investigated. Animals were either treated acutely with LPS (2 mg kg^–1) or cyclosporin (20 mg kg^–1) on dioestrus day 1 and 2 or treated chronically over a period of 6 days (on alternate days with LPS, daily with CS). Chronic LPS treatment induced a state of constant dioestrus and decreased circulating concentrations of progesterone and oestradiol. Chronic CS treatment induced some irregularity in the 4-day vaginal smear pattern in a minority of animals and, while it had no effect on circulating concentrations of progesterone, oestradiol concentrations were suppressed compared with those measured in pro-oestrous animals. LH responses to GnRH were reduced in both perifused pituitary fragments and cultured pituitary cells obtained from animals pretreated with either LPS or CS. In contrast, a low dose of LPS (20 µg kg^–1) given over 6 days did not disrupt ovarian cycles and reduced, but did not abolish, the second phase primed LH response. Neither drug had a direct effect on the pituitary LH responses to GnRH, except that pituitary cells exposed to high doses of CS for periods greater than 48 h did show attenuated LH responses to GnRH. This finding was not paralleled with high doses of LPS. The differential count of ovarian follicles from histological studies showed that LPS treatment was associated with significantly fewer large preovulatory follicles, whereas animals treated with CS showed a similar distribution of follicular volumes compared with controls. Results suggest that the hypothalamic–pituitary control of ovarian function is impaired by both LPS and CS treatment, and LPS appears to have an additional effect in suppressing ovarian functions, possibly via an inhibitory action on steroidogenesis.