Neuroendocrine factors
Perturbations of gonadotropin secretion are one of the hallmarks of PCOS. The most commonly described abnormality is an elevated serum LH or an elevated LH/FSH ratio, an increased LH pulse frequency and increased LH pulse amplitude, an exaggerated response of LH to GnRH, and altered diurnal LH pulse frequency (Morales et al., 1996; Taylor et al., 1997). However, serum LH levels may be normal in up to 40 per cent of women with PCOS (Conway et al.,
1990). On the other hand, Lobo et al. reported that bioactive/immunoreactive LH ratio is elevated in PCOS, which means that increased LH bioactivity may be responsible for enhanced androgen production in the ovary of women with the syndrome (Lobo et al., 2002). It is a matter of debate whether the increase of gonadotropins, when present, is a primary abnormality of hypotha-lamic-pituitary axis or the cause is dysregulation of the feedback signalling. Recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulsatility, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens (McCartney et al., 2002). In fact, both spontaneous ovulation or exogenous progesterone administration are associated with normalization of LH secretion in PCOS women (Taylor et al., 1997). Obesity may to some extent exaggerate the abnormal LH secretory pattern. A negative correlation between LH and body weight in PCOS has been found and obese PCOS women are characterized by significantly lower LH concentrations than non-obese PCOS women. Interestingly, in very obese PCOS women LH concentrations frequently resemble the normal range (Morales et al., 1996). Potential factors involved in the different LH secretion between obese and non-obese PCOS women may be elevated insulin concentrations, since significant correlations between LH and insulin has been found in PCOS women.
Obesity, as well as PCOS, is also characterized by increased opioid system activity, and studies in vitro and in vivo have shown that ß-endorphin is able to stimulate insulin secretion (Feldman et al., 1983; Pasquali and Casimirri, 1993). Moreover, an inhibition of opioid tone may induce a decreased hyperin-sulinaemia in PCOS women as a consequence of reduced insulin secretion and improved hepatic clearance (Fulghesu et al., 1993). In addition, ß-endorphin administration reduces LH release in normal women but not in PCOS women, suggesting a condition of ß-endorphin resistance in PCOS.
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