Role of galanin in the regulation of somatotrope and gonadotrope function in young ovulatory women

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.

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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

Ky²,

Hg³

et al. 2000

“…Galanin has thus been reported to act at the level of the pituitary to enhance the LH surge evoked by GnRH hypersecretion [18]; for review see 3], but also to inhibit LH release [19]. Similarly evidence suggests modulation of GH release, as demonstrated in rats [20, 21, 22], in humans [23]and bovine species [24]. …”

Section: Introductionmentioning

confidence: 93%

“…Apparently galanin can stimulate GH release directly at the level of the somatotropes [34]. In humans galanin enhanced the GH response to GHRH in vivo [23], whereas only basal but not GHRH-stimulated GH release from bovine pituitary fragments was enhanced by galanin [24]. On the basis of the dual effect of galanin both on pituitary LH and GH release in the bovine, these authors [24]suggested that one of the major physiological roles of galanin may be to regulate somatotrope-gonadotrope interactions at the hypothalamic and pituitary levels.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Porcine Pituitary Luteinizing Hormone Release by Galanin: Putative Auto/Paracrine Regulation

Elsaesser¹

2001

It has repeatedly been suggested that galanin acts within the anterior pituitary (AP) in an auto/paracrine manner to modulate luteinizing hormone (LH) release. Except for one recent report in the rat, evidence for this notion is absent. The purpose of this study was to investigate in the pig the effects of galanin on LH and growth hormone (GH) release and to evaluate putative local effects using various AP culture systems (monolayer, perifusion, reaggregates). Independent of age galanin dose dependently (0.05, 0.2, 1 µM) stimulated basal but not gonadotropin-releasing hormone (GnRH; ≧0.01 nM)-induced LH release. Neither basal nor GH-releasing hormone (GHRH)-stimulated GH release was affected at any age. Of 4 galanin receptor antagonists (0.2, 1 µM) tested C7 proved to have agonistic effects, whereas M40 and M15 (galantide) were ineffective in blocking galanin (0.2 µM)-induced LH secretion or affecting basal or GnRH-induced LH release. M32 [galanin (1–13) NPY (25–36) amide] inhibited (p ≤ 0.05) GnRH-induced LH release at doses of ≧2 µM, an effect which could be totally compensated by 1 µM galanin. However, the neuropeptide (NPY) antagonist BIBP 3226 (1 µM) partially overcame the effect of M32 (M32 is known to also bind to NPY receptors and NPY is inhibitory in the pig). In further studies using APs from preovulatory gilts a specific well-characterized galanin antiserum diluted 1:20 or 1:50 attenuated GnRH-induced LH release (p ≤ 0.05). However, an NPY antiserum (also affinity purified and at the same dilution) used as control unexpectedly inhibited GnRH (and galanin)-induced LH release as well, thus suggesting that attenuation of GnRH-induced LH release by galanin antiserum might be at least partly nonspecific. Furthermore 96-hour exposure of AP reaggregates to two types of porcine preprogalanin antisense oligodeoxynucleotides neither affected basal nor GnRH-induced LH release. In line with the failure to unequivocally prove paracrine effects of galanin, concentrations of galanin in AP cultures and AP culture medium were very low (≤2 pg galanin/10⁵ AP cells). In conclusion the present study provides some evidence to ascribe a hypophysiotropic role to galanin in regulating LH but not GH secretion in the pig. The study also points to the critical role of appropriate controls when trying to prove auto/paracrine control mechanisms within the anterior pituitary. Our findings do not provide convincing evidence to support the notion that intrapituitary galanin is involved in the fine tuning of LH secretion, at least in the preovulatory pig.

“…This effect has been demonstrated in rats treated with pharmacological doses of the peptide intracerebroventricularly [10,19,20], sub cutaneously [21] and intravenously [14,20], Recent stud ies in humans have reported a specific physiological role of galanin in the regulation of GH secretion [14,15,21,22], The mechanism underlying this action of galanin is unknown. Evidence seems to suggest that galanin may act at the hypothalamic level [5], Furthermore, strong evidence has been reported show ing the colocalization of galanin and luteinizing hormone (LH)-releasing hormone (LHRH) in preoptic hypotha lamic neurons [23,24], Administration of galanin into the brain evokes LH release in rats [25], possibly acting either via receptors in the median eminence or directly on pitu itary gonadotrops [26,27], In fact, some in vitro studies have reported that galanin elicits LH by enhancing LHRH secretion from hypothalamic fragments and/or by acting directly on cultured anterior pituitary cells.…”

Section: Introductionmentioning

confidence: 99%

Modulation by Galanin of Growth Hormone and Gonadotropin Secretion from Perifused Pituitary and Median Eminence of Prepubertal Male Calves

Baratta

Saleri²,

Mascadri³

et al. 1997

Self Cite

Galanin is widely distributed in the peripheral and central nervous system and has been indicated as a putative hypothalamic-hypophysiotropic hormone. This study was performed to investigate the effects of galanin on both growth (GH) and luteinizing hormones (LH) from pituitaries of young male calves. Pituitary slices (P, 500 µm in thickness) were perfused alone or coincubated with median eminence terminals (ME) in DMEM-F12 plus BSA 0.1% and antibiotics. The perifusion chambers were kept in equilibrium for 150 min, and medium samples were collected every 10 min for 240 min and stored at –20 °C until the measurement of LH and GH levels. Basal GH release increased up to 60% after galanin infusion (p < 0.01 vs. baseline levels) for 60 min in P alone; in P + ME coincubation, galanin-stimulated GH secretion was further increased by up to 200%. Basal LH release in chambers with P was significantly increased (up to 25%; p < 0.05) for 70 min after galanin infusion; P + ME coincubation showed a galanin-mediated increase in LH release of up to 50%. GH and LH responsiveness to exogenous GH-releasing hormone and gonadotropin-releasing hormone was not significantly modulated by galanin in our experimental model. In conclusion, galanin is demonstrated to have a significant stimulatory role in the secretion of GH and LH, with a combined action at both the hypothalamic and pituitary levels.