Testicular endocrine function in GH receptor gene disrupted mice

The consequences of disruption of GH receptor gene in GH receptor knockout mice on testicular function were evaluated. Adult male GH receptor knockout mice and their normal siblings were divided in to two subgroups and treate d with either saline or ovine LH (0.3 mug/g BW) in saline. One hour after s aline or LH administration, blood was obtained via heart puncture. Plasma I GF-I, LH, FSH, PRL, androstenedione, and testosterone levels were measured by RIAs. Testicular LH and PRL receptor numbers as well as pituitary LH bet a -subunit and testicular sulfated glycoprotein-2 mRNA levels were measured . Also, testicular morphometric analysis was performed. Unlike in normal, w ild-type mice, the circulating IGF-l was undetectable in GH receptor knocko ut mice. The plasma PRL levels were (P < 0.01) higher in GH receptor knocko ut mice than in their normal siblings. The basal LH secretion was similar i n normal and GH receptor knockout mice. However, the circulating FSH levels were lower (P < 0.001) in GH receptor gene disrupted mice. Administration of LH resulted in a significant (P < 0.001) increase in plasma testosterone levels in both GH receptor knockout and normal mice. However, this testost erone response was attenuated (P < 0.01) in GH receptor knockout mice. Plas ma androstenedione responses were similar in both GH receptor knockout and normal mice. Testicular LH and PRL receptor numbers were significantly decr eased in GH receptor knockout mice. The results of the morphometric analysi s of the testis revealed that the Leydig cell volume per testis was reduced in mice with GH receptor gene disruption. The steady-state of LH beta -sub unit and testicular sulfated glycoprotein-2 mRNA levels were not different in GH receptor knockout mice relative to their normal siblings. The present in vivo study demonstrates that in GH receptor knockout mice, LH action on the testis in terms of testosterone secretion is significantly attenuated and suggests that this is due to a decrease in the number of testicular LH receptors. The reduced number of PRL receptors may contribute to the dimini shed responsiveness of testicular steroidogenesis to LH by decreased abilit y to convert androstenedione to testosterone. These changes are most likely due to the absence of circulating IGF-I. These findings provide evidence t hat systemic IGF-I plays a major modulatory role in testicular endocrine fu nction.