Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey.
To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.
Giussani
D A
DA
Laboratory for Pregnancy and Newborn Research, Cornell University College of Veterinary Medicine, Ithaca, New York 14853-6401, USA.
Jenkins
S L
SL
Mecenas
C A
CA
Winter
J A
JA
Pedro
J G
JG
Farber
D M
DM
Goland
R S
RS
Nathanielsz
P W
PW
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000735:Androstenedione / Q000494:pharmacology*; D000818:Animals; D004958:Estradiol / Q000097:blood; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007275:Injections, Intravenous; D008253:Macaca mulatta / Q000502:physiology*; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000502:physiology*
D000735:Androstenedione; D004958:Estradiol; D000324:Adrenocorticotropic Hormone