Projections of the Estrogen Receptor-Immunoreactive Ventrolateral Hypothalamus to Other EstrogenReceptor-Immunoreactive Sites in Female Guinea Pig Brain

Abstract

The ventrolateral hypothalamus in female guinea pigs includes an estrogen receptor dense region adjacent to the ventromedial hypothalamus. This region is reciprocally connected with other estrogen receptor-containing areas suggesting that steroid hormone receptor-containing cells may be directly linked. Phaseolus vulgaris leucoagglutinin, an anterograde tract tracer, was specifically placed in this region with the aim of labeling some projections from estrogen receptor-containing neurons. These projections were colocalized immunocytochemically with the distribution of estrogen receptor-containing cells. Dense ventrolateral hypothalamic innervation was observed in some regions also containing a high concentration of estrogen receptor-containing cells. These regions included the medial preoptic area, the bed nucleus of the stria terminalis, the ventrolateral hypothalamus anterior and posterior to the injection site, and the midbrain central gray. A low density of ventrolateral hypothalamic fibers and terminals was observed in two regions rich in estrogen receptors, the amygdala and the arcuate nucleus. In general, ventrolateral hypothalamic fibers and terminals were present in all regions where estrogen receptors were found except the medial thalamus and habenular region. Labeled terminal boutons and perineuronal baskets were found around estrogen receptor-containing cells in most regions which contained estrogen receptor-containing cells. These close appositions were suggestive of synaptic contacts, suggesting that the ventrolateral hypothalamus may influence steroid-dependent behaviors via the modulation of estrogen receptor-containing cells. Furthermore, ventrolateral hypothalamic projections may include direct connections with estrogen receptor-containing cells, suggesting the presence of a network of interconnected estradiol-sensitive neurons involved in the regulation of estradiol-dependent functions.

Estrus Phase Differences in Female Rats in Morphine Antinociception Elicited From the Ventrolateral Periaqueductal Gray

“…The vlPAG supports mu opioid-mediated antinociception that is subject to sex differences (Krzanowska & Bodnar, 1999;Krzanowska et al, 2002) and to important organizational and activational roles of gonadal sex hormones in modulating intracerebral morphine antinociception (Cataldo et al, 2005;Krzanowska et al, 2002). Immunocytochemical (Hoffman et al, 1996;Turcotte & Blaustein, 1999), ultrastructural (Commons et al, 2000) and neurophysiological (Kow et al, 2002) evidence all demonstrate a close inter-relationship between the vlPAG and the reception of input from hypothalamic sites sensitive to circulating gonadal hormones, particularly related to the modulation of enkephalin gene expression (Priest et al, 1995;Romano et al, 1988Romano et al, , 1989Romano et al, , 1990. The present experiment's demonstration of greater magnitudes of morphine antinociception elicited from the vlPAG in female rats during proestrus relative to estrus and met-diestrus provides further confirmation of these previous studies, and underscores the importance of controlling the phase of the estrus cycle when performing studies examining sex differences in opioid antinociception.…”

“…First, hypothalamic changes in sex hormone levels across the estrus cycle in females include the turning on enkephalin genes to a greater degree than in males (Priest et al, 1995;Romano et al, 1988Romano et al, , 1989Romano et al, , 1990. Second, the estrogen-receiving ventromedial hypothalamic enkephalinergic neurons that eventually project to estrogen-binding PAG neurons (Turcotte & Blaustein, 1999) are absent following hypothalamic lesions (Hoffman et al, 1996). Third, mu opioids facilitate excitation in vlPAG cells via interactions with NMDA (Kow et al, 2002).…”

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

“…Inputs to and projections from the VMHvl have been mapped in several studies using classical techniques in rodents (e.g. CTb and PHAL, (36)(37)(38)(39)(40)(41)(42)(43)(44). However, these techniques are unable to distinguish genetically-defined cell populations within VMHvl, which is heterogeneous (9).…”

Neonatal and Adult Gonadal Hormone Manipulations Enhance Morphine Analgesia Elicited from the Ventrolateral Periaqueductal Gray in Female Rats

“…Hypothalamic enkephalinergic neurons, sensitive to changes in sex hormone levels, turned on enkephalin genes in females to a greater degree than males (Priest, Eckersell, & Micevych, 1995;Romano, Harlan, Shivers, Howells, & Pfaff, 1988;Romano, Mobbs, Howells, & Pfaff, 1989;Romano, Mobbs, Lauber, Howells, & Pfaff, 1990), and eventually projected to estrogenbinding PAG neurons (Turcotte & Blaustein, 1999), a pathway that was eliminated by hypothalamic lesions (Hoffman, Dohanics, Watson, & Wiegand, 1996). µopioids facilitated excitation in vlPAG cells through interactions with N-methyl-D-aspartate (NMDA) (Kow, Commons, Ogawa, & Pfaff, 2002), and the ultrastructural arrangement of the µ-opioid receptor with GABAergic periaqueductal gray (PAG) neurons or PAG projection neurons labeled retrogradely from the medulla indicated that µ-opioid receptor ligands both acted to inhibit the former, and acted directly on the latter (Commons, Aicher, Kow, & Pfaff, 2000).…”