The Consequences of Altered Somatotropic System on Reproduction1

Abstract

Although the primary control of gonadotropin secretion is by the hypothalamic GnRH and the gonadal function is controlled by the pituitary gonadotropins and prolactin, the emerging evidence suggests a vital role of the somatotropic axis, growth hormone (GH), and insulin-like growth factor-I (IGF-I) in the control of the pituitary and gonadal functions. It has been shown that GH deficiency, GH resistance, and experimental alterations in IGF-I secretion modify folliculogenesis, ovarian maturation, ovulation, and pregnancy, and in the male, GH/IGF-I plays an important role in spermatogenesis and the Leydig cell function. The primary focus of this review is to examine the role of GH/ IGF-I on the onset of puberty, fertility, pituitary, and gonadal endocrine functions. A number of studies have revealed that fertility is affected in GH-deficient dwarf and in IGF-I gene-ablated mice, possibly due to subnormal function of either the pituitary gland or the gonads. In the female GH receptor gene knockout (GHR-KO) mice, there was impairment in follicular development, ovulation rate, sexual maturation, production of and responsiveness to pheromonal signals, and the corpus luteum function. In IGF-I-deficient male GHR-KO mice, puberty is delayed, spermatogenesis is affected, and neuroendocrine-gonadal function is attenuated. Similarly, in some of the human Laron syndrome patients, puberty is delayed due to GH resistance. These data suggest that, in addition to GnRH and gonadotropins, GH/IGF-I influences the pituitary and gonadal functions in animals and humans.

Single-gene mutations and healthy ageing in mammals

“…Most of the laboratory mice used for contemporary research are derived from animals that have been domesticated as much as 100 years ago or even earlier and thus have been subjected for hundreds of generations to deliberate or inadvertent selection for genotypes (and epigenetic mechanisms) that favour thriving and fecundity under very artificial conditions of constant availability of food and little need or opportunity for physical activity. In some of the long-lived mouse mutants, puberty is delayed and fecundity reduced (for a review of data on Ghr2/2 mice, please see [73]). Interestingly, age of puberty and litter size in these mutants resemble the characteristics of normal mice derived from animals recently caught in the wild [74].…”

A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model

“…While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors. A mutation (lit) in the murine GHRH-R gene is associated with a loss of receptor function that leads to low systemic GH and IGF-I levels and to small body size (Jansson et al, 1986;Godfrey et al, 1993;Lin et al, 1993) but does not affect androgen levels (reviewed in Chandrashekar et al, 2004).…”

Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

“…penile size and risk of cryptorchidism) (3,5,6,7,8). The clinical observations are supported by histological studies identifying GH and IGF1 receptors in Leydig, Sertoli, and germ cells as well as in the accessory reproductive glands (1,9,10). A central hypothalamic/pituitary effect of GH has also been suggested including the stimulation of gonadotropin secretion (1,11,12,13).…”

“…The clinical observations are supported by histological studies identifying GH and IGF1 receptors in Leydig, Sertoli, and germ cells as well as in the accessory reproductive glands (1,9,10). A central hypothalamic/pituitary effect of GH has also been suggested including the stimulation of gonadotropin secretion (1,11,12,13). Finally, GH/IGF1 activity mayA common genetic polymorphism is deletion of the entire exon 3 sequence (GHRd3 isoform).…”

“…A growing body of evidence has pointed to the possibility that growth hormone (GH) and its primary downstream mediator insulin-like growth factor 1 (IGF1) may be important for normal male reproductive function (1). The influence of GH/IGF1 activity seems to involve reproductive hormone levels (2, 3), semen characteristics (2,4) and phenotype (e.g.…”