Developmental aspects of the hypothalamic-pituitary-adrenal axis

Area of Science:

• Reproductive endocrinology
• Fetal development
• Adrenocortical function

Background:

• Ovine fetal adrenal and pituitary glands are functional early in gestation.
• Zona glomerulosa matures mid-gestation, producing most fetal aldosterone, but lacks responsiveness to stimuli.
• Zona fasciculata is immature and unresponsive to ACTH early in gestation.

Purpose of the Study:

• To investigate the maturation of the ovine fetal hypothalamic-pituitary-adrenal (HPA) axis.
• To explore the role of cortisol in the maturation of the fetal adrenal cortex.
• To understand the functional development of the ovine HPA axis leading up to parturition.

Main Methods:

• Histological examination of fetal adrenal cortex.
• Measurement of fetal blood hormone levels (aldosterone, cortisol).
• Assessment of adrenal gland responsiveness to stimuli (K+, angiotensin II, ACTH) during gestation.

Main Results:

• Zona glomerulosa is morphologically mature by mid-gestation but unresponsive to stimuli until late gestation.
• Zona fasciculata is immature and unresponsive to ACTH early in gestation, contributing minimally to fetal cortisol.
• Zona fasciculata cells mature later in gestation, increasing cortisol production and responsiveness to ACTH.
• HPA axis maturation occurs in the last fifth of gestation.

Conclusions:

• Cortisol may play a local role in the maturation of fetal zona fasciculata cells.
• Maturation involves increased responsiveness to ACTH and resetting of cortisol's negative feedback on the HPA axis.
• The developmental trajectory of the ovine HPA axis and its hormonal changes parallel the pubertal maturation seen in humans.