The effect of growth hormone, growth factors and their binding globulins, on ovarian responsiveness

Intraovarian regulation and the potentiating effect of growth hormone, growth factors and their binding globulins on theca and granulosa cell response to gonadotropins has been demonstrated. This may have a significant impact in ovulation inducing therapy, in the understanding of some ovulatory disorders such as the polycystic ovarian syndrome, and in the pathogenesis of the hyperstimulation syndrome. Recently 3 observations claimed that GH administration increased ovarian sensitivity to gonadotropin stimulation, while one author, investigating ovulatory patients in an IVF program, could not demonstrate such an effect. This contradictory finding could be explained by our demonstration that anovulatory patients with 'poor response' and a low GH reserve either need excessive amounts of gonadotropins to obtain an acceptable response, or despite higher doses of hMG respond inadequately. The combined administration of GH and hMG to such patients resulted in good ovarian response despite a significantly lower dose of hMG. In patients with a good GH reserve the addition of GH had no significant effect on hMG dosage or response. Such tests may serve as preliminary differentiating indicators of ovarian sensitivity to hMG in poor responders and may help to select patients who may benefit from the combined GH-hMG therapy. However the role of growth factors in ovarian modulation must not be overestimated, since we also demonstrated, that follicular stimulation, ovulation and conception can occur in a 'Laron Dwarf', a condition characterized by elevated GH, absence of GH receptors, and lack of IGF-1. It can thus be concluded that IGF-1 is not obligatory for normal follicular development, but may play a permissive modulating role in ovarian function. This hypothesis endorses the possibility that pathologies leading to an imbalance of growth factors and their binding globulins may augment ovarian response to both FSH and LH resulting in enhanced follicular development, excessive androgen production and finally in the formation of a typical polycystic ovary with all the clinical consequences. These new insights may permit a cause related therapy for PCOD.