Pituitary and Testicular Function in Growth Hormone Receptor Gene Knockout Mice

Abstract

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 (i.p.) 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.

Integration mechanisms of transgenes and population fitness of GH transgenic fish

“…The infertility in female mice transgenic for the PEPCK.bGH gene construct is due to luteal failure, which in turn appears to be caused by inadequate PRL secretion after mating [61]. In studying the GH receptor gene knockout (GHR-KO) mice, Chandrashekar et al found that the circulating LH response to GnRH treatment was significantly attenuated, and basal and LH-stimulated testosterone release from the isolated testes of GHR-KO mice were decreased [62]. In GH receptor (GHR) and GH-binding protein (GHBP) knockout (KO) mice, the number of follicles per ovary was markedly reduced, and both the reproductive function and ovulation rate are measurably decreased compared with wild-type animals.…”

Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration

“…Inactivation of the GHR gene results in severe postnatal growth retardation, greatly decreased levels of IGF-1, and elevated levels of circulating GH. 1,2 The transcription factors Stat5a and Stat5b are highly conserved and serve overlapping and mostly redundant roles. However, pubertal growth of Stat5b Ϫ/Ϫ males, but not females, is reduced.…”

Aging-related characteristics of growth hormone receptor/binding protein gene-disrupted mice

“…The reduced testicular growth and possible impairment of spermatogenesis could be due to the reduced levels of plasma FSH seen in the GHR/BP j/j mice (Chandrashekar et al 2001). Basal levels of plasma LH and testosterone were similar in GHR/BP j/j and +/+ male mice, but the LH and testosterone responses to administration of a single dose of gonadotropin releasing hormone were significantly attenuated in the GHR/BP j/j mice (Chandrashekar et al 1999). Intratesticular levels of testosterone were essentially the same between GHR/BP j/j and +/+ males, but the basal in vitro release of testosterone by salinetreated testes obtained from GHR/BP j/j mice was significantly less than for saline-treated testes obtained from +/+ mice, as was the testosterone response to LH treatment, either by the isolated testes or by the intact animal (Chandrashekar et al 1999(Chandrashekar et al , 2001.…”

“…Absolute weights of the pituitary, testis, seminal vesicle, ventral prostate and epididymis were dramatically decreased, despite significantly increased levels of circulating prolactin (Keene et al 2002;Chandrashekar et al 1999 and. Fertility was also decreased, perhaps as a result of the hyperprolactinemia, although the number of testicular PRL receptors was decreased (Chandrashekar et al 1999 and.…”