Growth Hormone and Insulin-Like Growth Factor I Treatment Increase Testicular Luteinizing Hormone Receptors and Steroidogenic Responsiveness of Growth Hormone Deficient Dwarf Mice*

Abstract

To test the hypothesis that insulin-like growth factor (IGF-I) is required for the in vivo development of testicular Leydig cell function, either recombinant human GH [(hGH) (1.5 micrograms/g BW) or recombinant IGF-I (1 microgram/g BW) was injected three times daily into immature Snell dwarf mice (dw/dw) and into phenotypically normal control (Dw/-) for 7 days. In dw/dw mice hGH enhanced significantly body, liver, kidney, and testicular weight. In addition, hGH increased testicular LH receptors and the acute steroidogenic response to human CG, but there was no significant effect on basal plasma testosterone or plasma LH levels. The effects of IGF-I in body and kidney weight were less pronounced than those produced by hGH, but its effects on testicular weight and LH receptors, as well as on the acute steroidogenic response to human CG, were similar to that observed after hGH treatment. In Dw/- mice hGH had no effect on either body or organ weight or on testicular function, despite the fact that it induced a significant increase in plasma IGF-I levels. These results indicated that IGF-I is able to induce the maturation of Leydig cell function and that the effects of hGH on the testis are probably mediated by IGF-I. They also suggest that the delayed puberty associated with GH deficiency or resistance is most likely related to an IGF-I deficiency.

Growth Hormone Advances Spermatogenesis in Premature Rats Treated with Gonadotropin-Releasing Hormone Agonist.

“…Odell and Swerdloff reported that GH facilitated the testicular response to LH and increased the number of LH receptors in premature hypophysectomized rats [6]. Similar effects of GH mediated by insulin-like growth factor I (IGF-I) were reported by Chatelain et al using GH-deficient mice [7]. Recently, we reported that, in isolated Leydig cells, the amount of testoReceived: January 13, 1999 Accepted: June 11, 1999 Correspondence to: Kenji OHYAMA, M.D., Department of Clinical Nursing, Yamanashi Medical University, 1110, Shimokato, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan sterone production stimulated by hCG was greater in GH-pretreated premature rats than in control rats [8] .…”

“…5. In GnRHatreated rats, the counts of round spermatids (steps [1][2][3][4][5][6][7][8] were about half that of control rats and those of mature elongated spermatids (steps 15-19) were approximately 20%. Although counts of spermatids in GnRHa + GH-treated rats were also significantly lower than in control rats (p<0.01), those of elongated spermatids (steps 9-19) were significantly In GnRHa+GH-treated rat elongated spermatids were noticeably increased compared with the tubules of GnRHa-treated rat.…”

“…In GnRHa-treated rats, the number of spermatocyte was less than 80% of control rats, and the numbers of round and acrosome phase spermatids (steps [1][2][3][4][5][6][7][8][9][10][11][12][13][14] were approximately 40-50% of controls, and the number of mature spermatids (steps 15-19) were noticeably decreased to less than 20%. In GnRHa+GH-treated rats, the number of spermatocytes was gradually decreased with advancement of stage in spermatogenic cycle from 95% to 85%.…”

“…In GnRHa+GH-treated rats, the number of spermatocytes was gradually decreased with advancement of stage in spermatogenic cycle from 95% to 85%. The numbers of round and acrosome phase spermatids (steps [1][2][3][4][5][6][7][8][9][10][11][12][13][14] were approximately 60% of controls, and the number of mature spermatids were 40-45%. In other words, under the condition of gonadotropin deprivation, loss of germ cells is evident at several stages of development, that is, in mitosis of spermatogonia to spermatocyte, in meiosis of spermatocyte to spermatids and in the stage from acrosome to mature phase of spermatids.…”

“…Concerning the mechanism of GH action, the relevance of IGF-I to testicular function is suggested by many observations indicating that both Leydig and Sertoli cells produce and contain specific IGF-I receptors [25][26][27][28][29] and that IGF-I increases LH receptor and steroidogenic response to hCG in GH-deficient mice [30]. These findings would suggest that GH directly or GH mediated by IGF-I is involved with testicular testosterone action.…”