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Gender Modulates Sequential Suppression and Recovery of Pulsatile Growth Hormone Secretion by Physiological Feedback Signals in Young Adults

Division of Endocrinology and Metabolism (J.D.V., J.K.), Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905; Departments of Human Services (A.L.W., J.W., L.W.) and Internal Medicine (L.F., A.L.W.), General Clinical Research Center, University of Virginia, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

The basic mechanisms that drive the renewal of GH pulses in the human are not understood. Recent ensemble models predict that pulse regeneration requires quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new burst by rebound GHRH release. We reasoned that related principles might explain why women consistently maintain higher-amplitude GH secretory bursts than men. Accordingly, the present study tests the hypothesis that gender modulates the successive dynamics of GH feedback and escape in the morning fasting, when GH pulses are larger in women. To this end, we infused single iv pulses of recombinant human (rh) GH (0, 1, and 3 µg/kg) in eight young men and six women on separate randomly ordered mornings fasting and quantitated serial inhibition and recovery of GH secretion by frequent sampling, immunochemiluminometry, a deconvolution procedure, and regularity analysis. Statistical contrasts revealed gender-comparable peak concentrations and kinetics of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less feedback suppression of GH secretory-burst mass; (2) more irregular patterns of GH release during negative feedback; and (3) 12-and 14-fold greater postnadir rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit somatostatin outflow than men.

In summary, negative feedback induced by near-physiological GH pulses unmasks prominent gender-related contrasts in hypothalamo-pituitary autoregulation in young adults. A frugal but sufficient explanation of the ensemble outcomes is that women sustain greater hypothalamo-pituitary agonist input than men.

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