Short-term fasting suppresses leptin and (conversely) activates disorderlygrowth hormone secretion in midluteal phase women - A clinical research center study

Short term fasting activates the corticotropic and somatotropic, and suppre sses the reproductive, axis in men. Analogous neuroendocrine responses are less well characterized in women. Recently, we identified a negative associ ation between the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH secretion in older fed women. In the present study, we inv estigated the impact of acute nutrient deprivation on pulsatile GH and LH s ecretion and mean leptin concentrations in eight healthy young women in the sex-steroid replete milieu of the midluteal phase of the normal menstrual cycle. Volunteers underwent 24-h blood sampling during randomly ordered, sh ort term (2.5-day), fasting vs, fed sessions in separate menstrual cycles. Pulsatile GH and LH secretion over 24 h was quantified by deconvolution ana lysis, nyctohemeral rhythmicity was quantified by cosinor analysis, and the orderliness of the GH or LH release process was quantified by the approxim ate entropy statistic. By paired statistical analysis, a 2.5-day fast faile d to alter mean (pooled) 24-h serum concentrations of LH, progesterone, est radiol, or PRL, but increased cortisol levels more than 1.5-fold (P = 0.000 3). Concurrently, mean (pooled) serum leptin concentrations fell by 75% (P = 0.0003), and insulin-like growth factor I (IGF-I; P < 0.05) and insulin d ecreased significantly (P = 0.0018). In contrast, the daily pulsatile GH se cretion rate rose 3-fold (P < 0.001). Amplified daily GH secretion was attr ibutable mechanistically to a 2.3-fold rise in GH secretory burst mass, ref lecting an increased GH secretory burst amplitude (P < 0.01). The GH half-l ife, duration of GH secretory bursts, and GH pulse frequency did not vary d uring short term fasting. The disorderliness of GH release increased signif icantly with nutrient restriction (P = 0.005). The mesor and amplitude of t he nyctohemeral serum GH concentration rhythm also rose with fasting (P < 0 .01), but the timing of maximal serum GH concentrations did not change. Thus, short-term (2.5-day) fasting during the sex steroid-replete midluteal phase of the menstrual cycle in healthy young women profoundly suppresses 24-h serum leptin and insulin (and to a lesser degree, IGF-I) concentration s, augments cortisol release, but fails to alter daily LH, estradiol, or pr ogesterone concentrations. In contrast, the GH axis exhibits strikingly amp lified pulsatile secretion, increased nyctohemeral rhythmicity, and marked disorderliness of the release process. We conclude that the somatotropic ax is is more evidently vulnerable to short-term nutrient restriction than the reproductive axis in steroidogenically sufficient midluteal phase women. T his study invites the question of whether normal (nutritionally replete) GH secretory dynamics can be restored in fasting women by human leptin, insul in, or IGF-I infusions.