*Geek Box: Insulin and Androgens in PCOS
It is important to reiterate that insulin resistance in PCOS is observed in both lean PCOS phenotypes and PCOS phenotypes with obesity, particularly visceral/central adiposity. This is important because it indicates that the defective functionality of insulin and androgens, as elements of the pathophysiology of PCOS, have some internal origins.
In women, androgens are secreted by the adrenal glands and the ovaries and stimulated by adrenocorticotropic hormone [ACTH] and luteinizing hormone [LH], respectively. Both ACTH and LH are released from the pituitary gland. Generally, when LH levels are high, the ovaries become desensitised to LH. However, insulin acts to counterbalance this desensitising effect, thus maintaining responsiveness of the ovaries to the stimulatory actions of LH. In the context of elevated LH, this potentiates the synthesis of androgens by the ovaries.
It has long been established that elevated insulin drives ovarian androgen production, and that elevated androgens adversely affect ovulatory function. Typically, this is looked at as a causal chain, i.e., insulin>androgens>ovarian function, with an emphasis on the stimulatory effect insulin has on LH promoting androgen ovarian production. We could consider this an indirect effect of insulin on ovarian function.
Yet there is also evidence of a direct effect of insulin stimulating ovarian cells [theca and granulosa cells] through insulin receptors on these cells, i.e., that hyperandrogenic anovulation may be caused be elevated insulin and insulin binding with these cells. However, currently there is stronger evidence for the chain of elevated insulin > LH > ovarian androgen secretion > ovarian/ovulatory dysfunction.