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Sex steroids modulate reproduction by altering the response of steroid-activated opioid circuits in the hypothalamus and limbic system, by inducing release of endogenous opioids and activation of their cognate receptors. Many studies have concentrated on steroid regulation of exogenous opioid peptides, but steroids also have important actions on opioid receptors inducing receptor trafficking. Opioid receptors are G protein-coupled receptors and their activation catalyzes the exchange of GTP for GDP initiating intracellular signaling cascades. Kinetics of G protein activation were studied using [(35)S]GTPgammaS binding. Catalytic amplification, the number of G proteins activated per occupied receptor, was used as a measure of receptor/transducer amplification. The present study examined whether estrogen and progesterone treatment altered the kinetics of nociceptin opioid receptor (ORL1) in plasma membranes from the medial preoptic area and mediobasal hypothalamus. These hypothalamic regions are important in the gonadal steroid hormone regulation of sexual receptivity. In the mediobasal hypothalamus, estrogen increased ORL1 (B(max)) receptor number 2-fold and maximal GTPgammaS binding (E(max)) 3.9-fold. Subsequent progesterone treatment further increased ORL1 E(max )6.9-fold above baseline, despite a 2-fold decrease in the catalytic amplification factor. In the medial preoptic area, estrogen alone did not increase E(max), but both estrogen and progesterone were able to increase ORL1 B(max) 2.2-fold and E(max) 3-fold, despite having a 3-fold decrease in the catalytic amplification factor. These effects are interesting because they indicate actions of steroids that increase the number of ORL1 but decrease the catalytic amplification suggesting that the steroid effects on opioid receptors are complex and may involve modulation by other signals.

The degree of variation in structure of neurohypophyseal nonapeptides is reviewed and contrasted with the striking conservation in the structure of somatostatin across a range of vertebrate phylogeny. The distribution of neuropeptides has been most thoroughly studied in the central nervous system of the rat. Preliminary interspecies comparisons of the distribution of neuropeptides suggest that certain peptidergic elements found to be abundant in some species are poorly represented in the rat. Other peptidergic elements seem not to vary significantly between species.

Localization of enkephalins and opiate binding sites in the central nervous system of rats has been reported by several authors. These studies did not reveal an extensive enkephalinergic system in the hypothalamo-hypophyseal axis of rats. The present paper reports on an extensive enkephalinergic system in the cat hypothalamo-hypophyseal system. Sections of paraformaldehyde fixed cat hypothalami were incubated with anti-methionine enkephalin serum, anti-vasopressin serum, and anti-oxytocin serum. Immunohistochemical localization of methionine enkephalin fibers and terminals in the median eminence, hypophyseal stalk, and pars nervosa was similar, but not identical to the distribution of vasopressin and oxytocin in these structures. Neuronal perikarya localized with the three antisera in the nucleus supraopticus and nucleus paraventricularis were of a similar size and morphology. In cats treated with colchicine prior to sacrifice, the anti-methionine enkephalin serum revealed a group of periventricular cell bodies. Cell bodies were not localized in this area with anti-vasopressin or anti-oxytocin sera. The functional significance of such an extensive enkephalinergic system in the cat hypothalamo-hypophyseal axis is discussed.

Publisher Summary This chapter reviews some aspects of the distribution of presently characterized neuropeptides revealed by immunohistochemical techniques. The distribution of neuropeptides as revealed by immunohistochemical techniques suggests two varieties of neural circuits in which the peptides play a role. The first of these generalized systems is thought to participate in neuroendocrine regulation, as the peptides are found in high concentrations in terminals adjacent to vascular elements that drain either to the anterior pituitary or to systemic circulation. Peptides released from such neurohemal sites may act as hormones upon target cells. Alternatively, they may act via axo-axonic interactions with other peptidergic terminals that liberate “true” hormones. Neuropeptides are also found in circuits of neurons engaged in interneuronal communication.