Relative Sensitivity and Responsivity of Serum Cortisol and Two Adrenal Androgens to -Adrenocorticotropin-(1–24) in Normal and Obese, Nonhirsute, Eumenorrheic Women*
SURAT KOMINDR,
BRYAN R. KURTZ,
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 ACTH-(l–24) threshold dose and the response slopewere determined for cortisol (F), 4-androstenedione (A), anddehydroepiandrosterone (DHEA) in 10 normal and 16 obese eumenorrheicnonhirsute women matched for age. Each woman received 1 mg dexamethasoneat 2300 h and again at 0700 h the next morning. At 0700 h, acontinuous ACTH-(l- 24) infusion was begun at an initial doseof 30 ng/1.5 m2 body surface area-hr. The ACTH infusion ratewas doubled every hour for 5 consecutive h to a maximum doseof 480 ng/1.5 m2. h. Blood samples were collected for steroidassays before the infusion and at the end of each hour. TheACTH threshold dose was defined as the dose that produced asteroid response significantly above the basal level. The ACTHthreshold dose for serum F and DHEA stimulation was not differentbetween the groups, but the threshold dose for A was significantlylower in the obese women. Basal and stimulated serum DHEA toF ratios were significantly higher in the obsese women. In bothgroups, the mean F response slope was significantly higher thanthat for DHEA, which, in turn, was significantly higher thanthat for A. The mean DHEA response slope was significantly greaterin the obese women. The F and A response slopes were not differentbetween the groups. We conclude that 1) the relative responsivityof the steriods to ACTH was the same in both groups: F >DHEA > A; 2) in the obese women, the ACTH threshold dosefor F stimulation was lower (greater sensitivity) than for DHEAor A stimulation; and 3) in the obese women, the ACTH thresholddose for A was significantly lower (increased sensitivity) andthe slope of the DHEA response to ACTH was steeper (greaterresponsitivity) than in normal women.
* This study was conducted in The University of Tennessee ClinicalResearch Center at Memphis, which is supported by Grant RR-211from the General Clinical Research Center Program of the NIH.This work was also supported in part by NIH Grant AM-31312-02from the USPHS and NRSA GrantAM-07405.
Postdoctoral research fellow in Endocrinology. Present address:Department of Medicine, Ramathibodi Hospital, 6 Rama Road, Bangkok4, Thailand.
Sponsored by the Clinical Research Center Medical Student ResearchFellowship.
Present address: Department of Biochemistry, University of TexasHealth Center, Tyler, Texas 75710.
Received July 11, 1985.
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