New modalities for understanding dynamic regulation of the somatotropic (GH) axis: explication of gender differences in GH neuroregulation in the human.
BACKGROUND
Neuroendocrine regulation of the somatotropic (GH) axis is under the direction of hypothalamic signals, intrapituitary mechanisms, and multi-level feedback control. Consequently, understanding the regulation of the physiologically pulsatile mode of GH release in vivo is a substantial challenge.


OBJECTIVE
To present and review several new modalities designed to unmask novel features of physiological regulation of the GH axis. To this end, I emphasize gender differences in the control of pulsatile GH release, while highlighting the new approaches to uncovering such differences.


METHODS
Human volunteers.


METHODS
Novel investigative modalities include: (1) a high-sensitivity chemiluminescence GH assay capable of measuring 0.002 microgram/l of GH when utilized with a new discrete variance model for assay data reduction; (2) the technique of standardized linear regression to compare GH measures in men versus women; (3) the application of so-called deconvolution analysis, which is designed to estimate underlying rates of pulsatile hormone (GH) secretion as well as hormone half-life from a given plasma GH concentration profile; (4) an approximate entropy (ApEn) statistic to quantify the regularity or orderliness of hormone release, by assigning a single non-negative number that is a measure of the pattern reproducibility in the data; and (5) the evolution of network models to represent the physiological connections and feedback activities of the GH axis.


RESULTS
The foregoing new methodologies have collectively uncovered prominent gender differences in the regulation of the GH axis, which encompass: (i) higher mean serum GH concentrations due to greater GH secretory burst mass in women than men; (ii) relatively reduced suppressibility of GH by oral glucose administration due to greater GH secretory burst mass in women compared to men, with no apparent gender differences in the frequency of GH secretory bursts or the GH half-life in plasma; (iv) a remarkably higher degree of irregularity or disorder in the GH release process in women or female rats compared to male counterparts, indicating significantly reduced pattern reproducibility in the female; (v) an approximately two-fold greater sensitivity of men compared to women to the negative effects of age and increased percentage body fat and the positive impact of physical fitness on mean serum GH concentrations; and (vi) the ability of a multinodal network to capture the feedback relationships observed in vivo among GHRH, somatostatin, GH secretion, and GH and IGF-I negative feedback.


CONCLUSIONS
New analytical modalities for understanding dynamic regulation of the GH axis disclose a wide array of specific, prominent, and quantifiable gender differences in the physiological control mechanisms that direct this important neuroendocrine axis.
Veldhuis
J D
JD
Department of Internal Medicine, University of Virginia Health Sciences Center, National Science Foundation Center for Biological Timing, Charlottesville 22908, USA.
D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D012727:Sex Characteristics
D019382:Human Growth Hormone