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)α in the MPO and for ERβ 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 ERα, 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.

Expression of mRNAs Encoding Receptors That Mediate Stress Signals in Gonadotropin-Releasing Hormone Neurons of the Mouse

“…Together these studies provide substantive evidence that a subpopulation of GnRH neurons express CRH receptors in the mouse, and that GnRH neurons may be a direct target for CRH neurons. These observations are consistent with electron microscopic data [13] but do not agree with the work of Hahn et al [24], who failed to detect CRH-R1 transcripts in rat GnRH neurons by double-label in situ hybridization. This may represent species differences or reflect the different sensitivities of the two techniques employed.…”

Comparative study of the sources of neuronal projections to the site of gonadotrophin-releasing hormone perikarya and to the anteroventral periventricular nucleus in female rats

“…Various stressors suppress the pulsatile release of LH in rats (Blake, 1975;Rivier et al, 1986;Dong et al, 1994;Nagatani et al, 1996;Goubillon and Thalabard, 1996;Cagampang et al, 1997Cagampang et al, , 1999Tsukahara et al, 1999); such suppression may be mediated by central actions of CRH (Rivier and Vale, 1984;Ono et al, 1984;Rivier et al, 1986;Petraglia et al, 1987;Maeda et al, 1994;Roozendaal et al, 1996;Tsukahara et al, 1999). Our present findings of sparse retrograde labelling within the medial parvocellular PVN are consistent with the notion that CRH neurons at this site do not influence the reproductive axis by direct input to GnRH perikarya; this issue has been addressed in a previous report in which we presented evidence against the existence of direct CRH projections from the PVN to the vicinity of GnRH cells bodies in female rats (Hahn et al, 2003). In this context, it should be noted that several studies have indicated that CRH may not be required for stress-induced LH suppression (Rivest and Rivier, 1991;Akema et al, 1996;Jeong et al, 1999).…”

“…A role for the lateral septum in the modulation of motivated behavior associated with defense or aggression has been described (Clarke and Cummins, 1982;Kishore and Desiraju, 1990;Gavioli et al, 1999). Although a specific function for the ventral division of the lateral septum in estrous cycle control remains to be established, it should be noted that moderate to high levels of ER␣ and ER␤ expression are found at this site and also in the medial division of the BST (Shughrue et al, 1997;Li et al, 1997;Yokosuka et al, 1997;Laflamme et al, 1998;Zhang et al, 2002;Hahn et al, 2003); this is consistent with a postulated role for these regions in estrogen modulation of reproductive functions.…”

NeuroScholar\'s Electronic Laboratory Notebook and Its Application to Neuroendocrinology

“…In a related neuroanatomic study performed by a member of our group (Hahn et al, 2003), CRH neurons in the PVH were also examined in the context of their potential involvement in the suppression of reproductive function. Specifically, CRH has been implicated as a mediator for the inhibitory effects of stress (including glucoprivic stress) on reproductive function (Rivier and Vale, 1984;Tsukahara et al, 1999).…”

“…In the first example, we used the ELN to manage raw data and primary literature relevant to our own experiments, which concern the activation of brain areas during glucoprivation, a specific form of metabolic stress Watts, 2003, 2004). In our second example, we discuss potential uses of NeuroScholar to link this information to a related line of inquiry concerning how glucoprivic stress could suppress reproductive function (Hahn et al, 2003). These specialized examples serve to illustrate the use of the system in a specific context, and the reader is invited to apply the general design of the system for other scientific questions.…”