MINIREVIEW Effects of Growth Hormone Overexpression and Growth Hormone Resistance on Neuroendocrine and Reproductive Functions in Transgenic and Knock-Out Mice 2 (44434) ANDRZEJ BARTKE,* ,1 VARADARAJ CHANDRASHEKAR,* DANIEL TURYN,† RICHARD W. STEGER,* LUCIANO DEBELJUK,* TODD A. WINTERS,‡ JULIE A. MATTISON,* NATALIA A. DANILOVICH,* WILLIAM CROSON,* DANYEL R. WERNSING,* AND JOHN J. KOPCHICK¶ *Department of Physiology, School of Medicine, Southern Illinois University, Carbondale, Illinois 62901–6512; †Instituto de Quimica y Fisicoquimica Biologicas (UBA-CONICET), 1113 Buenos Aires, Argentina; ‡Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, Illinois 62901–4417; ¶Edison Biotechnology Institute and Department of Clinical Research, Ohio University College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701 Abstract. Transgenic mice overexpressing growth hormone (GH) exhibit alterations in the function of the hypothalamic-pituitary-gonadal (HPG) axis and the H-P-adrenal axis. Alterations in the turnover of hypothalamic neurotransmitters, in plasma hor- mone levels, and in regulation of their release are associated with reproductive defi- cits, particularly in females. Results reported after publication of our minireview on this subject provided evidence that GH-transgenic mice have increased binding of GH to GH binding proteins in plasma, are hyperinsulinemic and insulin resistant, and have major alterations in energy budgets with increased allocation to growth. Reduced life span and fertility of these animals may be related to insufficient allocation of energy to reproduction and maintenance. Growth hormone resistance induced by transgenic expression of an antagonistic bGH analog or by targeted disruption (knock-out, KO) of the GH receptor (GH-R) gene leads to dramatic suppression of plasma levels of insu- lin-like growth factor-1 (IGF-1), and dwarf phenotype due to reduced growth and in- creased adiposity. In both models of GH resistance, there are marked reproductive deficits in females, decline of breeding performance of males, and alterations in the function of the HPG axis. In GH-R-KO females, puberty is delayed, and litter size is reduced. Fetal weights are reduced whereas placental weights are increased, and the weight of newborn pups is reduced despite an increase in the length of gestation. In GH-R-KO males, copulatory behavior and fertility are reduced, plasma PRL is el- evated, and responses to lutenizing hormone releasing hormone (LHRH) in vivo and to LH in vitro are suppressed. However, reproductive deficits in GH-R-KO mice are Studies described in this review were supported by NIH (HD20001 and HD20033), by the Illinois Council on Food and Agricultural Research, and by SIU/C University Priorities and Interdisciplinary Initiative Program. 1 To whom requests for reprints should be addressed at Department of Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901–6512. E-mail: abartke@som.siu.edu 2 This article is an update of a previously published minireview (Proc Soc Exp Biol Med 206:345–359, 1994). 0037-9727/99/2222-0113$14.00/0 Copyright ©1999 by the Society for Experimental Biology and Medicine GROWTH HORMONE AND REPRODUCTION 113