Gestational hypoxia modulates expression of corticotropin‐releasing hormone and arginine vasopressin in the paraventricular nucleus in the ovine fetus

• Published in: Physiological reports 2016-01, Vol.4 (1), p.e12643-n/a
• Main Authors: Myers, Dean A., Singleton, Krista, Kenkel, Christy, Kaushal, Kanchan M., Ducsay, Charles A.
• Format: Article
• Language: English
• Subjects: Adaptation; Adrenal cortex; Adrenal glands; Adrenocorticotropic hormone; Altitude; Animals; Arginine Vasopressin - biosynthesis; Argipressin; AVP; Catheters; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - biosynthesis; Cortisol; CRH; Defense mechanisms; Enzymes; Female; Fetal Hypoxia - metabolism; Fetal Hypoxia - pathology; fetus; Fetus - metabolism; Fetus - pathology; Fetuses; Gestation; Hormones; Hybridization; Hypothalamic-pituitary-adrenal axis; Hypoxia; Intrauterine exposure; Maternal, Fetal and Neonatal Physiology; Menopause; mRNA; Neuroendocrinology; Original Research; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Physiology; Pituitary (anterior); Pregnancy; Premature birth; PVN; Sheep; Sheep, Domestic; Vasopressin
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.12643

Maturation of the fetal hypothalamo–pituitary–adrenocortical (HPA) axis is critical for organ maturation necessary for the fetus to transition to the ex‐utero environment. Intrauterine stressors can hasten maturation of the HPA axis leading to fetal growth restriction and in sheep, premature birth. We have previously reported that high‐altitude mediated, long‐term‐moderate gestational hypoxia (LTH) during gestation has a significant impact on the fetal HPA axis. Significant effects were observed at the level of both the anterior pituitary and adrenal cortex resulting in elevated plasma ACTH during late gestation with decreased adrenocortical expression of enzymes rate limiting for cortisol synthesis. As such, these fetuses exhibited the normal ontogenic rise in fetal plasma cortisol but an exaggerated cortisol response to acute stress. This study extended these findings to ACTH secretagogue expression in the PVN using in situ hybridization. We report that the expression of AVP but not CRH was increased in the medial parvocellular PVN (mpPVN) in the LTH fetus. This represented an increase in both AVP mRNA per neuron as well as an increase in AVP hybridizing neurons with no increase in mpPVN CRH neurons. LTH had no effect on PVN volume, area of CRH or AVP hybridization, thus LTH did not have a trophic effect on the size of the nucleus. In conclusion, there appears to be a switch from CRH to AVP as a primary ACTH secretagogue in response to LTH, supporting our previous findings of increased anterior pituitary sensitivity to AVP over CRH in the LTH fetus. Moderate gestational hypoxia impacts the function of the fetal hypothalamo–pituitary–adrenocortical (HPA) axis at both the level of anterior pituitary as well as adrenal cortex. We examined the effect of high‐altitude mediated, long‐term gestational hypoxia (LTH) on expression of the two key ACTH‐releasing factors, corticotropin‐releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamic paraventricular nucleus of the late gestation sheep fetus. We show that LTH in sheep induces an increased expression of arginine vasopressin (AVP) in the fetal paraventricular nucleus, while having no effect on corticotropin‐releasing hormone (CRH) expression.