Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary

Abstract

It has recently been shown that androgens increase the growth of immature follicles in the primate ovary. In the present study the effect of androgens on ovarian insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression was investigated. The study groups included five follicular phase, placebo-treated controls, and four testosterone- and three dihydrotestosterone (DHT)-treated rhesus monkeys. The treatment period was 5 days. Both testosterone and DHT treatment resulted in significant, 3-4-fold increases in IGF-I mRNA concentration in granulosa, thecal and interstitial compartments. Likewise, both androgens induced significant increases in the amount of IGF-I receptor mRNA, most notably in thecal cells and less markedly in granulosa and interstitium (P < 0.05). These changes in amounts of IGF system mRNA were documented in growing follicles up to the small antral (</=1 mm diameter) stage. Larger follicles were too few in number for significant comparisons. By contrast, amounts of ovarian insulin receptor mRNA were not appreciably altered by androgen treatment. These data suggest that IGF-I and its cognate receptor may mediate androgen-induced ovarian follicular and thecal-interstitial growth.

Disordered follicle development in ovaries of prenatally androgenized ewes

“…Preantral follicles from a number of species possess androgen receptors (Tetsuka et al 1995, Tetsuka & Hillier 1996, Hillier et al 1997, although the evidence for their presence in primordial follicles is less clear in the non-human primate . Nevertheless, short-term androgen treatment in vivo stimulates the early stages of follicle growth in primates, resulting in a significant increase in the number of small growing preantral and antral follicles (Vendola et al , 1999.…”

“…There are a number of paracrine and autocrine factors that are potential candidates for playing a role in controlling early folliculogenesis (McNatty et al 2000), including growth differentiation factor-9 (GDF-9), c-kit, inhibins, activins, anti-Müllerian hormone (AMH; otherwise known as Müllerian-inhibiting substance or MIS; Durlinger et al 1999) and insulin-like growth factors (IGFs). IGF-I is known to have mitogenic actions on, and to promote differentiation of, granulosa cells of antral and large preantral follicles in a number of mammalian species (Adashi et al 1985, Bergh et al 1991, Willis et al 1998 and data in primates suggest that IGF-I and its receptor mediate androgen-induced follicular growth (Vendola et al 1999).…”

“…The observation that 3-and 5-week-old prenatally androgenized female lambs possess enlarged ovaries with an increased number of follicles (West et al 2001), suggests that androgens may disrupt folliculogenesis in the androgenized sheep. There is additional evidence from other species (rats (Hillier & Ross 1979, Billig et al 1993, mice (Murray et al 1998), primates (Vendola et al , 1999 and humans (Hughesdon 1982) that the exposure to androgens disrupts the morphology and function of the ovary in post-pubertal mammals.…”

Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment

“…However, why is the normal level of T during the menstrual period (early follicular phase) positively correlated with TA in luteinised GCs? This finding may be related to the proliferation and development of GCs through the enhanced functions of FSH [37], GDF-9 [38], IGF-1 [39,40] and their receptors after stimulation by T during the early stage of follicular development. It has been widely reported that, at the early stages of follicular development, androgens produced by thecal cells under LH stimulation act as an enhancer of FSH-stimulated follicular differentiation.…”

Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men

“…Recently, it has been shown that IGF-I receptors may be regulated in part by the androgen receptor (AR) (Gori et al, 1999;Russo et al, 1999;Vendola et al, 1999). Testosterone (T) administration has been reported to increase serum IGF-I levels in both young and older men (Ferrando et al, 2002;Hobbs et al, 1993;Veldhuis et al, 1997;Weissberger and Ho, 1993).…”