The Gonadotropic Function of Insulin*

Abstract

We have reviewed the role of insulin in ovarian physiology. Clinical observations and experimental data strongly support the hypothesis that insulin possesses gonadotropic activity, when acting alone or with FSH or LH. This idea is further supported by the recent discovery of insulin in follicular fluid. The idea that insulin has gonadotropic function can explain a variety of clinical observations, which otherwise are difficult to understand. For example, manifestations of ovarian hypofunction (primary amenorrhea, late menarche, anovulation, low pregnancy rate, and early menopause) in IDDM can be understood if it is accepted that insulin is necessary for the ovary to reach its full steroidogenic potential. The idea that insulin affects ovarian steroidogenesis also helps to understand the observation that hyperandrogenism frequently accompanies each of the various insulin-resistant states, regardless of the latter's etiology (e.g. genetic deficiency in the number of insulin receptors, antiinsulin receptor antibodies, obesity, etc.). The explanation for this association is based on the idea that hyperinsulinemia intensifies ovarian steroidogenesis, which manifests clinically as hyperandrogenism. Continuous stimulation of the ovary by insulin over a long period of time possibly produces morphological ovarian changes, such as hyperthecosis or polycystic changes; these changes commonly are observed among women with insulin resistance. The effects of insulin on ovarian cells are mediated possibly through binding of the peptide to its own receptor or to the IGF-1 receptor (the specificity spillover phenomenon). The latter could be an important mechanism in cases of insulin resistance. Potential mechanisms underlying the gonadotropic activity of insulin include direct effects on steroidogenic enzymes, modulation of FSH or LH receptor number, synergism with FSH or LH, or nonspecific enhancement of cell viability. The gonadotropic function of insulin adds yet another note to what has been termed a symphony of insulin action. Further investigation into this new area may yield greater insights not only into normal ovarian physiology, but also into the pathogeneses of such diverse entities as PCO, obesity, diabetes mellitus, and the syndromes of insulin resistance and acanthosis nigricans.

Serum testosterone levels and breast cancer recurrence

“…15,16 Insulin stimulates the synthesis of androgens in the ovary. 19 Recently, high serum insulin levels have also been implicated, 13 with relative risks of the same magnitude as in the present study in which, however, the association was not statistically significant, possibly due to the small study size. Several studies have indicated that overweight patients, often characterized by hyperinsulinemic insulin resistant status and high sex hormones levels, have poorer survival.…”

Metabolic changes in early lactation and impaired reproductive performance in dairy cows

“…Among these is insulin, of which the stimulatory effect on progesterone production has been demonstrated in vitro on granulosa cells from pigs and cows [70]. Another factor seems to be IGF-I, which stimulates follicular growth and has also a clear link with the metabolic status of the cow.…”

Effect of a supplement rich in linolenic acid added to the diet of post partum dairy cows on ovarian follicle growth, and milk and plasma fatty acid compositions

“…In beef cows at maintenance, Thomas et al [6] showed that a soybean oil supplement was effective in increasing the number of medium sized follicles compared to a saturated fat (tallow) or a highly unsaturated fat (fish oil) supplement and this was associated with higher serum insulin. High insulin concentrations have been associated with increased granulosa cell proliferation [32] and improved follicle growth [11]. Thomas et al [6] hypothesised that fermentation conditions in the rumen were modified and that more propionate was available for the soybean oil cows and this explained the higher insulin levels observed.…”