Galanin’s Functional Significance in the Regulation of the Neuroendocrine Reproductive Axis of the Monkey

Abstract

Galanin stimulates the neuroendocrine reproductive axis in the rat, but whether galanin acts similarly in primate species is unknown. To test the hypothesis that galanin acts within the hypothalamo-hypophyseal axis to stimulate luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) secretion in the primate, galanin was administered either systemically or directly into the arcuate nucleus-median eminence of ovariectomized macaques (pigtailed or rhesus, respectively) that were maintained on estradiol. The mean plasma levels of LH were significantly elevated in pigtailed macaques after peripheral injection of galanin (2 mg) as compared with vehicle treatment. In rhesus monkeys, galanin (80 µM) administered by push-pull perfusion into the arcuate nucleus-median eminence did not significantly alter either GnRH or LH release. To determine whether in the monkey, as in the rat, subpopulations of medial forebrain GnRH neurons coexpress galanin mRNA, we used single- and double-label in situ hybridization and computerized imaging techniques. GnRH mRNA-containing cells were identified in both the medial and lateral forebrain of the female pigtailed macaque. No galanin mRNA expression was detectable in GnRH neurons located in either the medial preoptic area or mediobasal hypothalamus; however, within the substantia innominata a subset of GnRH mRNA-expressing neurons did coexpress galanin mRNA. Taken together, these results suggest that galanin induces LH release in primates, but galanin may not act directly on hypothalamic GnRH neurons. Presently, we have confirmed in another primate species the existence of GnRH gene expression in the lateral forebrain and discovered that a small subset of these neurons coexpress galanin. These particular cells may have a unique and as of yet undefined physiological function that is distinct from those GnRH neurons serving a hypophysiotropic function.

Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat

“…For example, neuropeptide Y (NPY) is a potent stimulator of food intake but inhibits reproduction in male rats (Pierroz, Catzeflis, Aebi, Rivier, and Aubert, 1996;Sainsbury, Schwarzer, Couzens, Jenkins, Oakes, Ormandy, and Herzog, 2002). POMC also decreases food intake and stimulates endocrine reproductive physiology (Finn, Pau, Spies, Cunningham, Clifton, and Steiner, 2000;Kalra, Dube, Pu, Xu, Horvath, and Kalra, 1999;Thornton, Cheung, Clifton, and Steiner, 1997). Conversely, central injections of galanin-like peptide (GALP) decrease food intake and body weight (Krasnow, Fraley, Schuh, Baumgartner, Clifton, and Steiner, 2003;Seth, Stanley, Dhillo, Murphy, Ghatei, and Bloom, 2003), but stimulate sex behavior and LH secretion in male rats (Fraley, Thomas-Smith, Acohido, Steiner, and Clifton, 2004;Krasnow et al, 2003).…”

Neuroendocrine Profiles in Galanin-Overexpressing and Knockout Mice

“…Galanin is coexpressed with GnRH in the forebrain of the female rat and has been linked to the control of LH release in rodents and primates [8, 33]. Curiously, LH levels were not altered with respect to controls in either GALTG or GALKO mice.…”

“…Of galanin’s many postulated roles, its regulation of neuroendocrine processes has been among the most comprehensively studied. Galanin is coexpressed with gonadotropin-releasing hormone (GnRH) in several species, and it has been shown to induce LH release in both rodent and primate species [6, 7, 8]. Galanin is also coexpressed with growth hormone-releasing hormone in the hypothalamic arcuate nucleus, and infusions of galanin stimulate the release of growth hormone [9, 10, 11].…”

Neuroendocrinology of nutritional infertility

“…It is almost certain that other neuropeptides will be shown to participate, too, including peptides yet to be discovered. For example, orexin, galanin, and galanin-like peptide all increase food intake and LH secretion (62,119,131,176,229), but a connection with nutritional infertility is yet to be determined. It has also been reported that melanocortins can increase circulating LH release (199) and sexual receptivity (44), but a role in nutritional infertility is doubtful (11,101,178).…”