Involvement of Central Corticotropin‐Releasing Factor (CRF) in Suckling‐Induced Inhibition of Luteinizing Hormone Secretion in Lactating Rats

The lack of ovulation and the inhibition of reproductive functions observed in many species during lactation is closely related to the intensity of the suckling stimulus. However, the mechanisms by which suckling inhibits hypothalamic GnRH and pituitary LH secretion in rats are still unclear. Since we recently demonstrated that suckling is a persistent stimulus to the adrenococortical system of the rat, we tested the hypothesis that suckling‐induced activation of central CRF release may mediate the associated inhibition of GnRH secretion. Lactating females were ovariectomized (OVX) on day 2 of lactation, and equipped with icv guide cannula on day 2 and indwelling jugular catheters on day 5 before testing on day 7. Lactating females were separated from their pups for 24 h prior to the suckling test with the following pretreatments: 1) icv injection with artificial CSF (aCSF) or a specific CRF antagonist, alpha‐helical CRF (9–41), (25μg/rat, CRF‐AX) 15 min prior to pup reunion or 2) iv injection of normal sheep serum (NSS) or CRF antiserum (CRF‐AB) 4 h prior to pup reunion. Plasma ACTH, LH and PRL concentrations were determined prior to and at various intervals after pup reunion. After 3 h of suckling, LH and PRL responses to a bolus injection of GnRH (10 ng/rat) were measured; a bolus injection of Angiotensin II (All, 5 μg/rat) was administered after 4 h to test for ACTH responses. Non‐lactating females injected with GnRH and All were used as controls. In animals treated icv with aCSF or iv with NSS, the suckling stimulus resulted in increased ACTH and PRL secretion with a decrease in LH release. Iv CRF‐AB abolished the increase in ACTH, but did not affect the increase in PRL nor the decrease in LH secretion. In contrast, and in support of our hypothesis, icv CRF‐AX abolished the suckling‐induced decline in LH secretion without altering the increase in PRL and ACTH secretion. Finally, we did not observe lactation‐related changes in LH (or PRL) responses to a bolus GnRH injection or in ACTH responses to All stimulation. Our results suggest that: 1) central CRF release is involved in the decrease in LH secretion which occurs following suckling in lactating females, and 2) the changes in LH secretion during suckling are not mediated by an effect of CRF at the median eminence or by acute changes in pituitary responsiveness to GnRH.