In fetal sheep, circulating cortisol increase during late gestation to abruptly rise 72 hours preceding birth. Although the surge in cortisol is thought to initiate the endocrine cascade which triggers parturition, it is not known what drives the prepartum rise in fetal cortisol. The first study tested the hypothesis that basal cortisol secretion is regulated by adrenocorticotropin (ACTH) which in turn, is controlled by arginine vasopressin (AVP). The fetus challenged with AVP increased plasma ACTH and cortisol concentrations. Pretreatment with an AVP V1 receptor antagonist blocked AVP-induced plasma ACTH cortisol but failed to alter basal ACTH or cortisol. To determine whether the gestational increase in fetal plasma cortisol is driven by pulsatile ACTH secretion, fetal blood was collected every 5 minutes for 2 hours at 133 days gestationand every four days until term (-146 days). Plasma cortisol and ACTH secretion were pulsatile in fetuses at all ages. Cortisol pulse frequency and amplitude increased near term; ACTH pulsatility was unchanged. Only 36% of the cortisol variance was statistically related to ACTH variance; pulse coincidence failed to exceed random association. To ascertain whether fetal pulsatile ACTH secretion is responsive to cortisol negative feedback, fetuses were infused with cortisol for 96 hours beginning at 133 days gestation. Cortisol treatment failed to suppress ACTH pulsatility. Increased pulsatile cortisol, but not ACTH, secretion was associated with birth in cortisol-treated and control fetuses. The data indicate that in the ovine fetus, constitutive cortisol secretion is not predominantly driven by ACTH secretion. Evidence suggests that ACTH and cortisol may be regulated by separate mechanisms during late gestation and cortisol may actually enhance constitutive pulsatile ACTH secretion. Concerning circadian rhythms, 24-h rhythms in uterine activity and endocrine secretion, ewes gave birth at night whether in short days or reverse short days; however, pinealectomized ewes delivered during the day. Thus, the mechanisms for photoperiodic time measurement and constitutive cortisol secretion are maintained to control time of day of birth in sheep.

LLU Discipline





Graduate School

First Advisor

Steven M. Yellon

Second Advisor

Charles A. Ducsay

Third Advisor

Thomas A. Linkhart

Fourth Advisor

Lawrence D. Longo

Fifth Advisor

Paul M. Plotshy

Degree Name

Doctor of Philosophy (PhD)

Degree Level


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

Hydrocortisone; Argipressin -- physiology; Labor -- physiology; Circadian Rhythm -- physiology; Adrenocorticotropic Hormone -- physiology; Sheep -- physiolog



Page Count

2 x; 199

Digital Format


Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.


Loma Linda University Electronic Theses and Dissertations

Collection Website



Loma Linda University. Del E. Webb Memorial Library. University Archives