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Pituitary and Testicular Function in Growth Hormone Receptor Gene Knockout Mice¹

Department of Physiology, Southern Illinois University School of Medicine (V.C., A.B.), Carbondale, Illinois 62901-6512; and Edison Biotechnology Institute, Molecular and Cellular Biology Program, Ohio University (K.T.C., J.J.K.), Athens, Ohio 45701

Address all correspondence and requests for reprints to: Dr. V. Chandrashekar, Department of Physiology, Life Science II Building, Southern Illinois University School of Medicine, Carbondale, Illinois 62901-6512.

The role of GH in the control of pituitary and testicular function is poorly understood. GH receptor gene knockout (GHR-KO) mice were recently produced. As these mice are good experimental animals to assess the influence of the effects of GH and insulin-like growth factor-I (IGF-I), the present studies were undertaken. Young adult male GHR-KO mice and their normal siblings were tested for fertility and subsequently injected (ip) with saline or GnRH (1 ng/g BW) in saline. Fifteen minutes later, blood was obtained via heart puncture. Plasma IGF-I, PRL, LH, and testosterone concentrations were measured by RIAs. In addition, the testicular testosterone response to LH treatment was evaluated in vitro. The results indicate that the absence of GH receptors (GHRs) was associated with an increase (P < 0.005) in plasma PRL levels, and circulating IGF-I was not detectable. Although the basal plasma LH levels were similar in GHR-KO mice relative to those in their normal siblings, the circulating LH response to GnRH treatment was significantly (P < 0.001) attenuated. Plasma testosterone levels were unaffected by disruption of the GHR gene. However, basal (P < 0.01) and LH-stimulated (P < 0.001) testosterone release from the isolated testes of GHR-KO mice were decreased. The rate of fertility in GHR-KO male mice was also reduced. These results indicate that the lack of GHRs (with GH resistance and lack of IGF-I secretion) induces hyperprolactinemia and alters the effect of GnRH on LH secretion as well as testicular function. Thus, GH and IGF-I influence pituitary and gonadal functions in male mice.

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