The neuroendocrine regulation and implications of pulsatile GH secretion: Gender effects

Gender differences are evident in many endocrine pathophysiologies. Like other neuroendocrine axes, regulation of the growth hormone (GH) axis is subject to prominent gender effects. Recent physiological studies demonstrate profound dependencies of mean 24-hour serum GH concentrations in men on age, body composition (e.g., percentage body fat), and physical fitness (e.g., as judged by maximal oxygen consumption). In contrast, age, body composition, and physical fitness are remarkably less significant determinants of mean serum GH concentrations in women of premenopausal age. Further investigations of the neuroendocrine mechanisms that regulate pulsatile GH release in young men and premenopausal women have shown 1.5 to 2.5 fold higher daily GH secretion rates in women. This gender difference is accounted for by a 2-fold greater mass of GH secreted per burst in women with no difference in GH secretory pulse frequency. Specific regulation of GH pulse amplitude is observed in women studied at different phases of the normal menstrual cycle with 2-fold higher serum GH peak heights in the late follicular phase. Endurance exercise training in women also doubles serum GH concentrations even in the early follicular phase. Ultrasensitive chemiluminescence and immunofluorometric GH assays capable of detecting 0.002 to 0.012 μg/L GH in peripheral blood show low basal rates of GH secretion in both men and women. Following glucose ingestion, women suppress their serum GH concentrations to < 0.70 μg/L and men to levels of < 0.07μg/L. Across a wide range of ages, the serum estradiol concentration is a strongly positive determinant of the mean serum GH level in mixed populations of men and women, as is the serum testosterone concentration in cohorts of men. Available clinical studies and data in experimental animals suggest that gender differences result from relatively increased GHRH release and/or action in the female associated with presumptively reduced somatostatin inhibitory tone. Moreover, target tissues of GH action show specific dependence of discrete responses (e.g., GH receptor, LDL receptor, cytochrome P-450, 1GF-I mRNA, etc., induction) on either a “male” (pulsatile) or “female” (continuous) GH release pattern. I conclude that prominent gender differences exist in the impact of age, body composition, and physical fitness on pulsatile GH release, and that such differences predominantly reflect the positive impact of sex-steroid hormones on the mass of GH secreted per burst and the degree to which GH release is suppressible by glucose.