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Developmental Aspects of Ovine Adrenal Adrenocorticotropic Hormone Receptor Expression

N. K. Valego, PhD

Y. Su, MD

J. Smith, MD, PhD

Departments of Obstetrics and Gynecology, Physiology, and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

J. C. Rose, PhD

Departments of Obstetrics and Gynecology, Physiology, and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Departments of Obstetrics and Gynecology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157; jimrose{at}wfubmc.edu

Objective: Maturation of adrenocortical function is important because a prepartum increase in fetal plasma glucocorticoids is required for survival after birth. Adrenal maturation may include alterations in the regulation of adrenocorticotropic hormone (ACTH) receptor expression. Therefore, we quantitated ACTH receptor expression in the ovine adrenal cortex during development and after manipulations to better understand the regulation of the adrenal receptor in vivo.

Methods: For the ontogeny study, adrenals were obtained from fetuses at different stages of development, and the cortical tissue was stored at -80C until total RNA was extracted. The ACTH binding studies were done on adrenal membranes obtained from fetuses at two different ages using I¹²⁵ (Phe-2, Nle-4) ACTH as the ligand. Plasma ACTH was measured by two-site immunoradiometric assay, and cortisol was measured by radioimmunoassay. ACTH receptor mRNA was quantitated by ribonuclease protection assay. The data were analyzed by analyses of variance.

Results: ACTH receptor mRNa level progressively increased in fetal life; relative changes in receptor mRNA and binding were similar (3.0-fold and 2.4-fold, respectively). Physiologic increases in fetal plasma cortisol decreased adrenal ACTH receptor mRNA concentration, and there was a strong (r² = 0.76, P < .002) linear relationship between fetal plasma ACTH concentration and receptor mRNA levels. Receptor mRNA stability increased in development, and message half-life was greater in adulthood than in fetal life.

Conclusion: The data suggest that developmental increases in receptor expression are part of the maturation process in the fetal adrenal and that plasma ACTH concentration plays a major role in regulating ACTH receptor mRNA levels in vivo.

Key Words: ACTH receptor • fetal • adrenal

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 1, 27-35 (2004)
DOI: 10.1016/j.jsgi.2003.07.006


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