Objective:To test the hypothesis that physiologic increases in fetal plasma 17β-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis.
Methods:Seventeen pregnant ewes and their fetuses were chronically catherized. At the time of surgery, the fetuses received implants that released 17β-estradiol (n = 5) alone or 17β-estradiol and androstenedione (n = 6), each at a rate of approximately 250 μg/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a “placebo” pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17β-estradiol and androstenedione.
Results:Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17β-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05).
Conclusions:Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.
1. Challis JRG, Brooks AN. Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep. Endocr Rev1989;10:182-204.
2.
2. Liggins GC, Fairclough RJ, Grieves SA, Kendall JZ, Knox BS. The mechanism of initiation of parturition in the ewe. Recent Prog Horm Res1973;29:111-159.
3.
3. Liggins GC, Kennedy PC, Holm LW. Failure of initiation of parturition after electrocoagulation of the pituitary of the fetal lamb. Am J Obstet Gynecol1967;98:1080-1086.
4.
4. McDonald TJ, Nathanielsz PW. Bilateral destruction of the fetal paraventricular nucleic prolongs gestation in sheep. Am J Obstet Gynecol1991;165:764-770.
5.
5. Myers DA, McDonald TJ, Nathanielsz PW. Effect of placement of dexamethasone adjacent to the fetal paraventricular nucleus on adrenocortical steroid hydroxylase messenger ribonucleic acid. Endocrinology1992;131:1329-1335.
6.
6. Wood CE. Insensitivity of near-term fetal sheep to cortisol: Possible relation to the control of parturition. Endocrinology1988;122:1565-1572.
7.
7. Anderson ABM, Flint AP, Turnbull AC. Mechanism of activation of glucocorticoids in induction of ovine parturition: Effect on placental steroid metabolism. J Endocrinol1975;66:61-70.
8.
8. Pomerantz DK, Nalbandov AV. Androgen level in the sheep fetus during gestation. Proc. Soc Exp Biol Med1975;149:413-416.
9.
9. Steele PA, Flint APF, Turnbull AC. Activity of steroid C-17,20 lyase in the ovine placenta: Effect of exposure to foetal glucocorticoid. J Endocrinol1976;69:239-246.
10.
10. Yu HK, Cabalum T, Jansen CA, Buster JE, Nathanielsz Pw. Androstenedione, testosterone, and estradiol concentrations in fetal and maternal plasma in late pregnancy in the sheep. Endocrinology1983;113:2216-2220.
11.
11. Liggins GC. Parturition in the sheep and the human. In: Coutinho EM, Fuchs F, eds. Physiology and genetics of reproduction. New York: Plenum Press, 1974:423-443.
12.
12. Saoud CJ, Wood CE. Modulation of ovine fetal adrenocorticotropin secretion by androstenedione and 17β-estradiol. Am J Physiol1997;272:R1128-R1134.
13.
13. Wood CE. Sensitivity of cortisol-induced inhibition of ACTH and renin in fetal sheep. Am J Physiol1986;250:R795-R802.
14.
14. Bell ME, Wood CE, Keller-Wood M. Influence of reproductive state on pituitary-adrenal activity in the ewe. Domest Anim Endocrinol1991;8:245-254.
15.
15. Saoud CJ, Wood CE. Ontogeny of pro-opimelanocortin post-translational processing in the ovine fetal pituitary. Peptides1996;17:55-61.
16.
16. Challis JRG, Patrick JE. Fetal and maternal estrogen concentrations throughout pregnancy in the sheep. Can J Physiol Pharmacol1981;59:970-978.
