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

Abstract

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...

Heterogeneity in the Basic Membrane Properties of Postnatal Gonadotropin-Releasing Hormone Neurons in the Mouse

“…immediate early genes, and neuropeptides, including GnRH itself (Hiatt et al, 1992;Merchenthaler et al, 1993;Porkka-Heiskanen et al, 1994;Wang et al, 1995;Gore et al, 1996;Simonian et al, 2000). We now provide direct evidence for functional heterogeneity in the basic membrane properties of these neurons.…”

Basal Testosterone Secretion and Response to Human Luteinizing, Follicle-Stimulating, and Growth Hormones in Culture of Cells Isolated from Testes of Infants and Children

“…Whether this could be attributed to lack of GH action in the testes at early infancy remains to be shown. However, several studies in rodents (37)(38)(39) and in non-human primates (7) show that the secretory role of the neonatal testes is critical for normal CNS function in adulthood.…”

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

“…Female rats have approximately five-fold higher co-expression of the galanin and GnRH neuropeptides within the same neurons than do male rats, and respond to hormone treatment in adulthood with increased colocalization [102]. Although male rats do not normally respond to hormone treatment with increased co-expression of galanin and GnRH, neonatal castration of male rats, followed by hormone treatment in adulthood, enables males to manifest the up-regulation of galanin and GnRH co-expression [102]. These findings by Merchenthaler et al suggest a sexually differentiated pathway for GnRH regulation that is active in female rats, but is unmasked in neonatally castrated male rats.…”