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Journal of Clinical Endocrinology & Metabolism Vol. 63, No. 4 860-864
doi:10.1210/jcem-63-4-860
Copyright © 1986 by the Endocrine Society.
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Relative Sensitivity and Responsivity of Serum Cortisol and Two Adrenal Androgens to {alpha}-Adrenocorticotropin-(1–24) in Normal and Obese, Nonhirsute, Eumenorrheic Women*

SURAT KOMINDR{dagger}, BRYAN R. KURTZ{ddagger}, MICHAEL STEVENS§, JAMES G. KARAS, JOYCE B. BITTLE and JAMES R. GIVENS

Department of Medicine, Division of Endocrinology, Section of Reproductive Medicine, University of Tennessee School of Medicine, Clinical Research Center Memphis, Tennessee 38163

Address requests for reprints to: James R. Givens, 951 Court Avenue, 340M, Memphis, Tennessee 38163.

The {alpha}ACTH-(l–24) threshold dose and the response slope were determined for cortisol (F), {Delta}4-androstenedione (A), and dehydroepiandrosterone (DHEA) in 10 normal and 16 obese eumenorrheic nonhirsute women matched for age. Each woman received 1 mg dexamethasone at 2300 h and again at 0700 h the next morning. At 0700 h, a continuous {alpha}ACTH-(l- 24) infusion was begun at an initial dose of 30 ng/1.5 m2 body surface area-hr. The ACTH infusion rate was doubled every hour for 5 consecutive h to a maximum dose of 480 ng/1.5 m2. h. Blood samples were collected for steroid assays before the infusion and at the end of each hour. The ACTH threshold dose was defined as the dose that produced a steroid response significantly above the basal level. The ACTH threshold dose for serum F and DHEA stimulation was not different between the groups, but the threshold dose for A was significantly lower in the obese women. Basal and stimulated serum DHEA to F ratios were significantly higher in the obsese women. In both groups, the mean F response slope was significantly higher than that for DHEA, which, in turn, was significantly higher than that for A. The mean DHEA response slope was significantly greater in the obese women. The F and A response slopes were not different between the groups. We conclude that 1) the relative responsivity of the steriods to ACTH was the same in both groups: F > DHEA > A; 2) in the obese women, the ACTH threshold dose for F stimulation was lower (greater sensitivity) than for DHEA or A stimulation; and 3) in the obese women, the ACTH threshold dose for A was significantly lower (increased sensitivity) and the slope of the DHEA response to ACTH was steeper (greater responsitivity) than in normal women.

* This study was conducted in The University of Tennessee Clinical Research Center at Memphis, which is supported by Grant RR-211 from the General Clinical Research Center Program of the NIH. This work was also supported in part by NIH Grant AM-31312-02 from the USPHS and NRSA Grant’AM-07405.

{dagger} Postdoctoral research fellow in Endocrinology. Present address: Department of Medicine, Ramathibodi Hospital, 6 Rama Road, Bangkok 4, Thailand.

{ddagger} Sponsored by the Clinical Research Center Medical Student Research Fellowship.

§ Present address: Department of Biochemistry, University of Texas Health Center, Tyler, Texas 75710.

Received July 11, 1985.




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