| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Articles |
Departments of Obstetrics and Gynecology (M.J.B., T.M.V., S.M.A., L.W.R., J.D.V.) and Internal Medicine (N.S., W.S.E., J.D.V.), General Clinical Research Center, Center for Biomathematical Technology, University of Virginia School of Medicine, Charlottesville, Virginia 22908; and Endocrine Section (A.I.), Medical Service Veterans Affairs Medical Center, Salem, Virginia 24153
Address all correspondence and requests for reprints to: J. D. Veldhuis, M.D., Division of Endocrinology, Department of Internal Medicine, P.O. Box 800202, University of Virginia School of Medicine, Charlottesville, Virginia 22908. E-mail: jdv{at}virginia.edu
Abstract
How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin’s inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17ß orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 µg/1.73 m2·h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 µg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10-4 interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 ± 6.1% (mean ± SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 ± 1 to 245 ± 35 pg/mL [42 ± 4 to 920 ± 110 pmol/L] (P < 10-4); decreased serum concentrations of LH (P = 0.018), FSH (P < 10-4), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 ± 0.07 to 0.87 ± 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin’s maximal suppression of GH by 89 ± 4.7% (P < 10-4 below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38–0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2–7.0) (estradiol) µg/1.73 m2/h (P < 10-4), denoting muting of somatostatin’s inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10-4). The foregoing effects were specific, because estrogen did not alter somatostatin’s dose-dependent enhancement (P < 10-4) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic.
In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin’s dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin’s reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.
This article has been cited by other articles:
 |
|
 |
|
  M. Cosma, J. Bailey, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis Pituitary and/or Peripheral Estrogen-Receptor {alpha} Regulates Follicle-Stimulating Hormone Secretion, Whereas Central Estrogenic Pathways Direct Growth Hormone and Prolactin Secretion in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Veldhuis, D. M. Keenan, and C. Y. Bowers Peripheral estrogen receptor-{alpha} selectively modulates the waveform of GH secretory bursts in healthy women Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1514 - R1521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, M. Cosma, D. Erickson, R. Paulo, K. Mielke, L. S. Farhy, and C. Y. Bowers Tripartite Control of Growth Hormone Secretion in Women during Controlled Estradiol Repletion J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2336 - 2345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Farhy, C. Y. Bowers, and J. D. Veldhuis Model-projected mechanistic bases for sex differences in growth hormone regulation in humans Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1577 - R1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, D. M. Keenan, A. Iranmanesh, K. Mielke, J. M. Miles, and C. Y. Bowers Estradiol Potentiates Ghrelin-Stimulated Pulsatile Growth Hormone Secretion in Postmenopausal Women J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3559 - 3565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition Endocr. Rev., April 1, 2006; 27(2): 101 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Veldhuis, J. M Patrie, K. Frick, J. Y Weltman, and A. L Weltman Administration of recombinant human GHRH-1,44-amide for 3 months reduces abdominal visceral fat mass and increases physical performance measures in postmenopausal women Eur. J. Endocrinol., November 1, 2005; 153(5): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, D. Erickson, K. Mielke, L. S. Farhy, D. M. Keenan, and C. Y. Bowers Distinctive Inhibitory Mechanisms of Age and Relative Visceral Adiposity on Growth Hormone Secretion in Pre- and Postmenopausal Women Studied under a Hypogonadal Clamp J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6006 - 6013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, L. Farhy, A. L. Weltman, J. Kuipers, J. Weltman, and L. Wideman Gender Modulates Sequential Suppression and Recovery of Pulsatile Growth Hormone Secretion by Physiological Feedback Signals in Young Adults J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2874 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Soares-Welch, L. Farhy, K. L. Mielke, F. H. Mahmud, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis Complementary Secretagogue Pairs Unmask Prominent Gender-Related Contrasts in Mechanisms of Growth Hormone Pulse Renewal in Young Adults J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2225 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, S. M. Anderson, A. Iranmanesh, and C. Y. Bowers Testosterone Blunts Feedback Inhibition of Growth Hormone Secretion by Experimentally Elevated Insulin-Like Growth Factor-I Concentrations J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1613 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-D. Qu, I. T. Gaw Gonzalo, M. Y. Al Sayed, P. Cohan, P. D. Christenson, R. S. Swerdloff, D. F. Kelly, and C. Wang Influence of Body Mass Index and Gender on Growth Hormone (GH) Responses to GH-Releasing Hormone Plus Arginine and Insulin Tolerance Tests J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1563 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Erickson, D. M. Keenan, L. Farhy, K. Mielke, C. Y. Bowers, and J. D. Veldhuis Determinants of Dual Secretagogue Drive of Burst-Like Growth Hormone Secretion in Premenopausal Women Studied under a Selective Estradiol Clamp J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1741 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Iranmanesh, C. Y. Bowers, and J. D. Veldhuis Activation of Somatostatin-Receptor Subtype-2/-5 Suppresses the Mass, Frequency, and Irregularity of Growth Hormone (GH)-Releasing Peptide-2-Stimulated GH Secretion in Men J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4581 - 4587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Erickson, D. M. Keenan, K. Mielke, K. Bradford, C. Y. Bowers, J. M. Miles, and J. D. Veldhuis Dual Secretagogue Drive of Burst-Like Growth Hormone Secretion in Postmenopausal Compared with Premenopausal Women Studied under an Experimental Estradiol Clamp J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4746 - 4754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Racine, K. V. Symons, C. M. Foster, and A. L. Barkan Augmentation of Growth Hormone Secretion after Testosterone Treatment in Boys with Constitutional Delay of Growth and Adolescence: Evidence against an Increase in Hypothalamic Secretion of Growth Hormone-Releasing Hormone J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3326 - 3331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, J. Patrie, L. Wideman, M. Patterson, J. Y. Weltman, and A. Weltman Contrasting Negative-Feedback Control of Endogenously Driven and Exercise-Stimulated Pulsatile Growth Hormone Secretion in Women and Men J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 840 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Biermasz, A. M. Pereira, M. Frolich, J. A. Romijn, J. D. Veldhuis, and F. Roelfsema Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E25 - E30. [Abstract] [Full Text]
|
|
|
|
|
|
E. Richmond, A. D. Rogol, D. Basdemir, O. L. Veldhuis, W. Clarke, C. Y. Bowers, and J. D. Veldhuis Accelerated Escape from GH Autonegative Feedback in Midpuberty in Males: Evidence for Time-Delimited GH-Induced Somatostatinergic Outflow in Adolescent Boys J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3837 - 3844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Svensson, J. D. Veldhuis, A. Iranmanesh, B.-A. Bengtsson, and G. Johannsson Increased Orderliness of Growth Hormone (GH) Secretion in GH-Deficient Adults with Low Serum Insulin-Like Growth Factor I J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2863 - 2869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Farhy, M. Straume, M. L. Johnson, B. Kovatchev, and J. D. Veldhuis Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory dynamics Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R753 - R764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gentili, T. Mulligan, M. Godschalk, J. Clore, J. Patrie, A. Iranmanesh, and J. D. Veldhuis Unequal Impact of Short-Term Testosterone Repletion on the Somatotropic Axis of Young and Older Men J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 825 - 834. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
