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Submitted on July 27, 2004
Accepted on February 13, 2005
Department of Human Services; Department of Internal Medicine, General Clinical Research Center, University of Virginia, Charlottesville, VA 22908
* To whom correspondence should be addressed. 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 (SS) 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: (a) infused single iv pulses of rh GH (0, 1 and 3 µg/kg) in 8 young men and 6 women on separate randomly ordered mornings fasting; and (b) 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 rh GH. However, women differed from men by way of: (i) 3.5 and 4.0-fold less feedback suppression of GH secretory-burst mass; (ii) more irregular patterns of GH release during negative feedback; and (iii) 12 and 14-fold greater post-nadir rebound-like GH secretion after rh GH pulses. Mechanistic analyses based upon a minimal feedback construct predicted that women generate higher endogenous secretagogue stimulation per unit SS 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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