Studies on the neuroanatomical basis for stress-induced oestrogen-potentiated suppression of reproductive function: evidence against direct corticotropin-releasing hormone projections to the vicinity of luteinizing hormone-releasing hormone cell bodies in female rats.

Abstract

Various studies implicate corticotropin-releasing hormone (CRH) as a mediator for the inhibitory effects of stress on reproduction. This study was designed to elucidate the underlying neuroanatomy. The retrograde tracer cholera toxin was picospritzed into the vicinity of the luteinizing hormone-releasing hormone (LHRH) perikarya. CRH neurones were examined for the tracer in the medial preoptic nucleus (MPO), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), central amygdaloid nucleus (CeM), parabrachial nucleus (PB) and additional locations. Retrograde label was not detected in CRH neurones at any of these sites; nevertheless, in the MPO and PB, abundant retrogradely-labelled perikarya intermingled with CRH neurones. In the BST, CeM and PVN, sites containing major CRH cell populations, retrogradely-labelled cells were scarce or absent; however, retrograde labelling was found in adjacent regions: lateral septum, medial amygdaloid nucleus and areas bordering the PVN. Double-label in situ hybridization for the mRNAs for LHRH and the CRH type-1 receptor (CRH-R1) identified the receptor transcript at sites rostral and lateral to the LHRH neurones (in the vertical and horizontal limbs of the diagonal band) but not in the LHRH neurones. Given the ability of oestrogen to potentiate stress-induced suppression of LH release, the identification of CRH neurones immunoreactive for oestrogen receptor (ER) alpha in the MPO and for ER beta in the caudal PVN may be significant. In this context, it is also noteworthy that CRH neurones within the MPO and PB which are, respectively, immunopositive and immunonegative for ER alpha, lie within the vicinity of retrogradely-labelled cells. The present findings suggest that the means by which CRH may mediate inhibitory effects of stressors on LH release do not involve direct CRH projections to LHRH neurones; the indirect means for such regulation, and the sites at which oestrogen may potentiate the inhibitory response, remain to be established.