Galanin: a hypothalamic-hypophysiotropic hormone modulating reproductive functions.

López, Francisco J.; Merchenthaler, Istvån; Ching, Melvin; Wisniewski, Miriam G.; Negro‐Vilar, A.

doi:10.1073/pnas.88.10.4508

Cited by 162 publications

(119 citation statements)

References 32 publications

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“…Modulation of the release of the anterior pituitary hormones prolactin, growth hormone, and luteinizing hormone by galanin is now well documented (6)(7)(8)(9)(10)(11)(12)(13) include (i) changes in the release of hypothalamic stimulating and inhibiting factors (e.g., TRH, GHRH, GnRH, dopamine, and SRIF), (ii) effects of hypothalamic galanin secreted into the portal circulation and acting directly on basal and/or stimulated hormone release from the lactotroph, somatotroph, or gonadotroph and (iii) locally synthesized and secreted galanin acting in an autocrine manner.…”

Section: Discussionmentioning

confidence: 99%

“…Recently galanin has been shown to be episodically released into the hypothalamo-pituitary portal circulation at concentrations in the nanomolar range (12), providing further evidence for its putative role as a modulator of pituitary function.…”

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confidence: 99%

“…Various studies have demonstrated effects of galanin on basal and stimulated release of prolactin (6,7), growth hormone (8)(9)(10)(11), and luteinizing hormone (12,13) either from dispersed pituitary cells or at the hypothalamic level modulating dopamine, somatostatin (SRIF; somatotropin releaseinhibiting factor), and gonadotropin-releasing hormone (GnRH) release into the portal circulation. Recently galanin has been shown to be episodically released into the hypothalamo-pituitary portal circulation at concentrations in the nanomolar range (12), providing further evidence for its putative role as a modulator of pituitary function.…”

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Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor.

Wynick

Smith

Ghatei

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

111

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Structure-activity studies demonstrate that galanin fragments 1-15 and 2-29 are fully active, whereas fragment 3-29 has been reported to be inactive, in a number of different in vivo models. M15, a chimeric peptide comprising galanin 1-13 and substance P 5-11, has recently been found to be a potent galanin antagonist. Galanin, a 29-amino acid peptide, was originally isolated from porcine intestine (1) and subsequently reported to be widely distributed in gut, pancreas, and the peripheral and central nervous systems (2, 3). Highest levels of galanin synthesis and storage occur within the hypothalamus in the median eminence (4), but it is also abundantly expressed in the anterior pituitary, where it has been shown to be estrogen inducible (5).Various studies have demonstrated effects of galanin on basal and stimulated release of prolactin (6, 7), growth hormone (8-11), and luteinizing hormone (12, 13) either from dispersed pituitary cells or at the hypothalamic level modulating dopamine, somatostatin (SRIF; somatotropin releaseinhibiting factor), and gonadotropin-releasing hormone (GnRH) release into the portal circulation. Recently galanin has been shown to be episodically released into the hypothalamo-pituitary portal circulation at concentrations in the nanomolar range (12), providing further evidence for its putative role as a modulator of pituitary function.In view of the high concentrations of galanin reaching or secreted by the anterior pituitary it is puzzling that a number of studies have failed to demonstrate anterior pituitary binding of [mono(125I)iodo-Tyr26]galanin (1251-Tyr-galanin) by membrane assay or by autoradiography in the rat or pig (14,15), although these studies demonstrated good thalamicand/or hypothalamic-specific galanin binding.Bartfai et al. (16) have recently synthesized a high-affinity galanin antagonist by fusing galanin 1-13 with substance P 5-11, which they termed M-15. This antagonist has been shown to be a potent inhibitor, at doses of 1 nM or less (with an IC50 of 0.1 nM), of the actions of galanin on the pancreas, smooth muscle, and hippocampus.The following studies demonstrate that galanin stimulates the release of prolactin from cultured anterior pituitary cells and that a specific galanin antiserum blocks basal prolactin secretion. The galanin antagonist M15 has no effect on basal or galanin-stimulated prolactin release. Using galanin 1251-labeled with the Bolton-Hunter (1251-BH) reagent at the N terminus, a single high-affinity galanin receptor in the pituitary is characterized. Unlike the brain/gut galanin receptor, the C-terminal part of the peptide is crucial for pituitary membrane binding. MATERIALS AND METHODSPituitary Dispersion. Anterior pituitaries were removed from randomly cycling female Wistar rats (Interfauna, Huntingdon, U.K.) immediately after death by decapitation and dispersed as described (17). Tissue was incubated while shaking at 37°C for 1 hr in Hanks' balanced salt solution (HBSS, GIBCO; containing 0.1% bovine serum albumin, pH 7.4) containing 0...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor.

Wynick

Smith

Ghatei

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

111

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“…during the estrous cycle (5), suggesting that GAL expression in LHRH-immunoreactive (LHRH-i) neurons is dependent on the steroid imprinting.…”

Section: For a Review) In This Respect We Have Observed Differentiamentioning

confidence: 99%

Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

Merchenthaler

Lennard

López

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4-to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility-i.e., gender-specific determination of LHRH neurons coexpressing GAL-was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of LHRH neurons that could synchronize their activity to control the estrous cycle in rats.Recent observations from our laboratory indicate that a subpopulation of luteinizing hormone-releasing hormone (LHRH) neurons in the rat brain also expresses galanin (GAL) (1). The incidence of colocalization exhibits a striking sex difference-i.e., in females =80% of the LHRH neurons contain GAL, whereas in males only 10-15% of these neurons synthesize this peptide (2). In situ hybridization studies have corroborated our earlier findings since GAL mRNA is colocalized with the decapeptide LHRH in LHRH neurons (3). It has been reported that estradiol has a profound effect on GAL gene expression in the pituitary and the hypothalamus (see ref. 4 for a review). In this respect, we have observed differential coexpression ofGAL in LHRH neuronsThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.during the estrous c...

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“…Of particular interest is a subpopulation of LHRH neurons that coexpresses the peptide galanin (2,19,20). Although little is known about the physiological significance of this coexpression, there is abundant evidence that galanin plays an important role in LH secretion (15,16,18,28). However, until now there was no direct evidence that the LHRH neurons containing galanin comprise a subpopulation that is active during periods of LH hypersecretion.…”

Section: Introductionmentioning

confidence: 97%

Triple-labeling method combining immunocytochemistry and in situ hybridization histochemistry: demonstration of overlap between Fos-immunoreactive and galanin mRNA-expressing subpopulations of luteinizing hormone-releasing hormone neurons in female rats.

Hrabovszky

Vrontakis²,

Petersen³

1995

J Histochem Cytochem.

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).We desaibe a sensitive technique combining dual-label immunocytochemistry (ICC) with isotopic in situ hybridization histochemistry (ISHH). We developed this technique to characterize the receptor andlor peptide content ofphenotypically identified neurons that express cell markers of neuronal activity (immediate early gene products) after physiological or pharmacological perturbation. Tissue was fted by perfusion with 4% paraformaldehyde in PBS, suaoseinfiltrated, and ayosectioned. Sections were stored in ayoprotectant or immediately hybridized. After smngent hybridization wash procedures, Eos and luteinizing honnonereleasing hormone (LHRH) neurons were visualized sequentially using immunocytochemistry. Finally, galanin mRNA

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Galanin: a hypothalamic-hypophysiotropic hormone modulating reproductive functions.

Cited by 162 publications

References 32 publications

Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor.

Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor.

Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

Triple-labeling method combining immunocytochemistry and in situ hybridization histochemistry: demonstration of overlap between Fos-immunoreactive and galanin mRNA-expressing subpopulations of luteinizing hormone-releasing hormone neurons in female rats.

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