Endocrinology, Vol 124, 1760-1767, Copyright © 1989 by Endocrine Society

ARTICLES

Pubertal changes in gonadotropin-releasing hormone and proopiomelanocortin gene expression in the brain of the male rat

JN Wiemann, DK Clifton and RA Steiner
Department of Obstetrics and Gynecology, University of Washington, Seattle 98195.

Pubertal development in mammals is in part attributable to a brain- dependent process, whereby increased pulsatile GnRH secretion leads to the awakening of the entire reproductive system. However, the brain mechanisms controlling this event are unknown. The apparent increase in GnRH secretion at puberty could reflect an autonomous change in the activity of GnRH neurons themselves or in the afferent networks leading to GnRH neurons. If there were a significant increase in the secretion of GnRH with puberty onset, we hypothesized that there would be a commensurate increase in the biosynthetic capacity of GnRH neurons to meet the increasing demand. We tested this hypothesis by comparing the level of cellular prepro-GnRH mRNA (GnRH mRNA) observed between prepubertal (25-day-old; n = 5) and adult (75-day-old; n = 4) male rats by in situ hybridization. We detected no significant change with puberty in GnRH mRNA signal levels in any of the anatomical areas examined, which included the vertical limb of the diagonal band of Broca, medial septum, lateral preoptic area, and medial preoptic area. Given the variance of our analytical technique, we determined that there was a greater than 90% probability that we would have detected a 20% increase in GnRH mRNA had there been one. Endogenous opioid peptides have been implicated in timing the onset of puberty in the rat, with the argument being that a loss in opioid tone could effect a disinhibition of GnRH secretion. One opioid peptide, beta-endorphin, is among several peptides cleaved from the precursor POMC. We hypothesized that with puberty, POMC neurons in the arcuate nucleus would have an attenuated capacity to produce beta-endorphin. We tested this hypothesis by comparing cellular pre-POMC mRNA (POMC mRNA) levels in the arcuate nuclei of prepubertal (n = 6) and adult (n = 7) male rats with in situ hybridization. We observed an increase in POMC mRNA levels with puberty; prepubertal rats had relative POMC mRNA signal levels of 119 +/- 10 grains/cell, while adult rats contained 167 +/- 12 grains/cell (P less than 0.02). This increase in cellular POMC mRNA was confined to the rostral portion of the arcuate nucleus. We conclude that the GnRH gene is fully expressed well before the time of normal puberty onset and that the increase in POMC mRNA that occurs with the onset of puberty may be important for the development of pulsatile GnRH secretion.

This article has been cited by other articles:

				F. Remmers, L. A. W. Verhagen, R. A. H. Adan, and H. A. Delemarre-van de Waal Hypothalamic Neuropeptide Expression of Juvenile and Middle-Aged Rats after Early Postnatal Food Restriction Endocrinology, July 1, 2008; 149(7): 3617 - 3625. [Abstract] [Full Text] [PDF]

				J. Liu, J. C. Garza, H. V. Truong, J. Henschel, W. Zhang, and X.-Y. Lu The Melanocortinergic Pathway Is Rapidly Recruited by Emotional Stress and Contributes to Stress-Induced Anorexia and Anxiety-Like Behavior Endocrinology, November 1, 2007; 148(11): 5531 - 5540. [Abstract] [Full Text] [PDF]

				F. J P Ebling The neuroendocrine timing of puberty Reproduction, June 1, 2005; 129(6): 675 - 683. [Abstract] [Full Text] [PDF]

				F. Gomez, S. Manalo, and M. F. Dallman Androgen-Sensitive Changes in Regulation of Restraint-Induced Adrenocorticotropin Secretion between Early and Late Puberty in Male Rats Endocrinology, January 1, 2004; 145(1): 59 - 70. [Abstract] [Full Text] [PDF]

				S. B. Seminara, S. Messager, E. E. Chatzidaki, R. R. Thresher, J. S. Acierno Jr., J. K. Shagoury, Y. Bo-Abbas, W. Kuohung, K. M. Schwinof, A. G. Hendrick, et al. The GPR54 Gene as a Regulator of Puberty N. Engl. J. Med., October 23, 2003; 349(17): 1614 - 1627. [Abstract] [Full Text] [PDF]

				K. Proulx, D. Richard, and C.-D. Walker Leptin Regulates Appetite-Related Neuropeptides in the Hypothalamus of Developing Rats without Affecting Food Intake Endocrinology, December 1, 2002; 143(12): 4683 - 4692. [Abstract] [Full Text] [PDF]

				S. B. Seminara, F. J. Hayes, and W. F. Crowley Jr. Gonadotropin-Releasing Hormone Deficiency in the Human (Idiopathic Hypogonadotropic Hypogonadism and Kallmann's Syndrome): Pathophysiological and Genetic Considerations Endocr. Rev., October 1, 1998; 19(5): 521 - 539. [Abstract] [Full Text]

				Y. P. Tang, M. L. Kashon, and C. L. Sisk Brain Region-Specific Regulation of Luteinizing Hormone-Releasing Hormone Messenger Ribonucleic Acid in the Male Ferret: Interactions between Pubertal Maturation and Testosterone Endocrinology, November 1, 1997; 138(11): 4740 - 4747. [Abstract] [Full Text] [PDF]