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This version published online on July 22, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0930
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Submitted on April 29, 2008
Accepted on July 11, 2008

Androgens May Mediate a Relative Preservation of IGF-1 Levels in Overweight and Obese Women Despite Reduced Growth Hormone Secretion

A Utz, A Yamamoto, P Sluss, J Breu, and K K Miller*

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 02114; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 02114; and MIT Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA, United States, 02139

* To whom correspondence should be addressed. E-mail: KKMiller{at}Partners.org.

Context: Obesity is characterized by reduced GH secretion, but data regarding IGF-1 levels and their determinants are conflicting.

Objective: To determine whether IGF-1 levels are reduced and to investigate determinants of GH and IGF-1 in healthy overweight and obese women

Design: Cross-sectional

Setting: General Clinical Research Center

Study Participants: 34 healthy women without pituitary/hypothalamic disease: 11 lean (BMI < 25 kg/m2), 12 overweight (BMI ≥ 25 kg/m2 and < 30 kg/m2) and 11 obese (≥ 30 kg/m2) women of comparable age (overall mean 30.7 ± 7.8 y).

Intervention: None

Main Outcome Measures: 24-h q 10 minute frequent sampling for GH, peak GH after GHRH-arginine stimulation, IGF-1, IGFBP-3, estrone, estradiol, testosterone, free testosterone, SHBG, HOMA-IR and abdominal fat.

Results: Mean 24-hour GH and peak stimulated GH were lower in overweight than lean and lowest in obese women. Mean IGF-1 levels trended lower in obese, but not overweight, compared with lean, women. Free testosterone was positively associated with IGF-1 (R=0.36, p=0.04) but not with GH measures. Visceral fat was the only determinant of mean 24-hour GH (R2=0.66, p<0.0001) and of peak stimulated GH (R2=0.63, p<0.0001), and mean 24-hour GH accounted for 39% of the variability of IGF-1 (p=0.0002), with an additional 28% (p<0.0001) attributable to free testosterone levels.

Conclusions: Despite a linear decrease in GH secretion and peak stimulated GH levels with increasing BMI in healthy overweight and obese women, IGF-1 levels were not commensurately reduced. Androgens may contribute to this relative preservation of IGF-1 secretion in overweight and obese women despite reduced GH secretion.
Key words: GH • IGF-1 • Testosterone • Obesity






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