Growth Hormone Enhances Follicle-Stimulating Hormone-Induced Differentiation of Cultured Rat Granulosa Cells*

Abstract

Suppression of serum GH levels in immature rats is associated with delayed onset of puberty and decreased ovarian steroidogenic responsiveness to FSH. To investigate possible direct effects of GH on the differentiation of ovarian cells, granulosa cells from hypophysectomized estrogen-treated rats were cultured with FSH in the presence or absence of GH for 3 days. FSH stimulated granulosa cell LH receptor formation and steroid production in a dose-dependent manner. Concomitant treatment with GH increased LH receptor content by enhancing the action of low doses of FSH without substantial increases in the maximal response. This increase was due to an elevation in the receptor number rather than changes in their affinity for hCG. At 3 ng/ml FSH, concomitant treatment with ovine or bovine GH increased LH/hCG binding in a dose-dependent manner, with 300 ng/ml GH increasing the FSH action by about 3-fold. LH receptors in the GH-treated cells were functional, as indicated by the enhanced cAMP production of these cells in response to LH treatment. The cellular protein content in the FSH-treated cultures was slightly increased by GH (18%), but cell number and viability were unaffected. The change in cell protein content could not account for the increases in the amount of LH receptors. In addition to its effects on LH/hCG receptor content, GH also augmented FSH-stimulated progesterone and 20 alpha-hydroxy-4-pregnen-3-one production in a dose-dependent manner, with 100 ng/ml GH causing significant increases in FSH-induced progesterone production. In contrast, GH treatment did not significantly affect FSH-stimulated estrogen production. The augmentating effects of GH on LH receptor formation and progestin biosynthesis were associated with an enhancement of FSH-stimulated cAMP production. In addition, GH increased forskolin- and 8-bromo-cAMP-induced LH receptor formation and progestin production. Thus, GH-augmented LH receptor induction and progestin biosynthesis may be due to both increased cAMP production and enhanced action of cAMP. The present data have demonstrated that GH augments gonadotropin-stimulated differentiation of ovarian granulosa cells, suggesting an important regulatory role of GH in follicular growth and pubertal development.

The role of growth hormone in male infertility

“…In addition to this, in a series of in-vitro studies, Adashi and his colleagues (1985a) found that incubation of granulosa cells with insulin and insulin-like growth factor-I (IGF-I) augmented their responses to stimulation by FSH. These studies have been confirmed and extended by others (Hammond et al, 1985;Davoren & Hsueh, 1986;Jia et al, 1986). Following the hypothesis that G H or IGF-I can facilitate granulosa cell responsiveness to gonadotrophins, a series of studies demonstrated that co-treatment with G H augmented the ovarian response to stimulation by gonadotrophins (Homburg et al.…”

Interaction between growth differentiation factor 9, insulin-like growth factor I and growth hormone on the in vitro development and survival of goat preantral follicles

“…GH may thus be particularly important in the recruitment of follicles and the initiation of oocyte growth, perhaps by adjusting nutritional status to the number of growing oocytes (20). Furthermore, GH has been shown to enhance cell proliferation and steroidogenesis of cultured granulosa cells in rats (21) and in cattle (22), pointing out an important role of this hormone in the regulation of follicular growth. Early studies assumed that IGF-I was the sole mediator of GH action in the ovary, since IGF-I or GH enhances steroid production to the same extent in rats (23) and GH usually increases follicular-luteal IGF-I in cows (24).…”

The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency

“…A considerable body of in vivo and in vitro evidence suggests the existence of a relationship between growth hormone (GH) and the reproductive system both in animals and humans (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). In fact, several studies have demonstrated that GH treatment increases ovary sensitivity to gonadotropin stimulation in infertile women with hyposensitive ovaries (12)(13)(14)(15)(16)(17)(18)(19).…”