Homeostatic joint amplification of pulsatile and 24-hour rhythmic cortisolsecretion by fasting stress in midluteal phase women: Concurrent disruption of cortisol-growth hormone, cortisol-luteinizing hormone, and cortisol-leptin synchrony

Short-term fasting as a metabolic stress evokes prominent homeostatic react ions of the reproductive, corticotropic, thyrotropic, somatotropic, and lep tinergic axes in men and women. Although reproductive adaptations to fastin g are incompletely studied in the female, nutrient deprivation can have maj or neuroendocrine consequences in the follicular phase. Unexpectedly, a rec ent clinical study revealed relatively preserved sex steroid and gonadotrop in secretion during short-term caloric restriction in the midluteal phase o f the menstrual cycle. This observation suggested that female stress-adapti ve responses might be muted in this sex steroid-replete milieu. To test thi s hypothesis, we investigated the impact of fasting on daily cortisol secre tion in healthy young women during the midluteal phase of the normal menstr ual cycle. Eight volunteers were each studied twice in separate and randoml y ordered short-term (2.5-day) fasting and fed sessions. Pulsatile cortisol secretion, 24-h rhythmic cortisol release, and the orderliness of cortisol secretory patterns were quantified. Within-subject statistical comparisons revealed that fasting increased the mean serum cortisol concentration sign ificantly from a baseline value of 8.0 +/- 0.61 to 12.8 +/- 0.85 mug/dL (P = 0.0003). (For Systeme International conversion to nanomoles per L, multip ly micrograms per dL value by 28.) Pulsatile cortisol secretion rose commen surately, viz. from 101 +/- 11 to 173 +/- 16 mug/dL/day (P = 0.0025). Augme nted 24-h cortisol production was due to amplification of cortisol secretor y burst mass from 8.2 +/- 1.5 to 12.9 +/- 2.0 mug/dL (P = 0.017). In contra st, the estimated half-life of endogenous cortisol (104 +/- 9 min), the cal culated duration of underlying cortisol secretory bursts (16 +/- 7 min) and their mean frequency (14 +/- 2/day) were not altered by short-term fasting . The quantifiable orderliness of cortisol secretory patterns was also not influenced by caloric restriction. Nutrient deprivation elevated the mean o f the 24-h serum cortisol concentration rhythm from 12.4 +/- 1.3 to 18.4 +/ - 1.9 mug/dL (P = 0.0005), without affecting its diurnal amplitude or timin g. Correlation analysis disclosed that fasting reversed the positive relati onship between cortisol and LH release evident in the fed state, and abolis hed the negative association between cortisol and GH as well as between cor tisol and leptin observed during nutrient repletion (P < 0.001). Pattern sy nchrony between cortisol and GPI as well as that between cortisol and LH re lease was also significantly disrupted by fasting stress. In summary, short-term caloric deprivation enhances daily cortisol secretio n by 1.7-fold in healthy midluteal phase young women by selectively amplify ing cortisol secretory burst mass and elevating the 24-h rhythmic cortisol mean. Augmentation of daily cortisol production occurs without any concomit ant changes in cortisol pulse frequency or half-life or any disruption of t he timing of the 24-h rhythmicity or orderliness of cortisol release. Fasti ng degrades the physiological coupling between cortisol and LH, cortisol an d GH, and cortisol and leptin secretion otherwise evident in calorie-suffic ient women. We conclude that the corticotropic axis in the young adult fema le is not resistant to the stress-activating effects of short-term nutrient deprivation, but, rather, evinces strong adaptive homeostasis both monohor monally (cortisol) and bihormonally (cortisol paired with GH, LH, and lepti n).