Endogenous release of CRH in stress has been associated with a dysfunctional reproductive endocrine axis. In the rhesus monkey, an inflammatory-like stress challenge in the luteal phase decreases luteal secretory function. Here, we tested the effectiveness of astressin B, a non-specific CRH receptor antagonist, in constraining the deleterious impact of a 10-day lipopolysaccharide (LPS) challenge on the menstrual cycle. Two protocols were carried out in 9 animals. In the first, the animals, after showing 2 normal consecutive control cycles, were injected daily for 10 days with LPS (75-125 µg/day) during the luteal phase of the cycle. The animals were followed through the 2 post-challenge cycles. The second protocol, carried in the following year, was identical to protocol 1, except that the animals were treated with astressin B (0.45 mg/kg) 1 h before each daily LPS challenge during the luteal phase. Blood samples were obtained daily to document cyclic hormones levels.

The LPS challenge significantly decreased luteal progesterone and LH release during the challenge cycle. Inhibition of luteal progesterone extended to the 2 successive post-challenge cycles. Astressin B treatment prevented luteal LH but not luteal progesterone decrease during the treatment cycle and restored normal progesterone secretion during the 2 post-treatment cycles. We conclude that the deleterious impact of a short-term inflammatory stress challenge on luteal function is far longer than the stress period itself. Systemic administration of astressin B accelerates the return to normal luteal function, presumably by restoring normal neuroendocrine regulation of gonadotropin secretion.