Fetal adrenal gland

Pomerantz, J.E., Li, C., Nathanielsz, P.W. and McDonald, T.J. (1996) Corticotropin-releasing hormone axons in the adrenal glands of fetal and postnatal sheep. J. Autonomic Nervous System 59: 87-90.

Unno, N., Wu, W.X., Ding, X.Y., Li, C., Man A Hing, W.K.H, and Nathanielsz, P.W. (1998) The effects of fetal adrenalectomy at 110 days gestational age and subsequent cortisol administration on CRH and AVP mRNA expression in the hypothalamic paraventricular nucleus of the ovine fetus. Dev. Brain Res. 106: 119-128.

Tame, J.D., Winter, J.A., Li, C., Jenkins, S.L., Giussani, D.A., and Nathanielsz, P.W. (1998) Fetal growth in the baboon during the second half of pregnancy. J. Med. Primatol. 27(5) 234-239.

Berghorn, K.A., Li, C., Nathanielsz, P.W. and McDonald, T.J. (2000) VIP innervation: Sharp contrast in fetal sheep and baboon adrenal glands suggests differences in developmental regulation. Brain Res. 877(2):271-280.

The fetal hypothalamo-pituitary-adrenal axis plays a central role in initiation of parturition and maturation of fetal organs for neonatal life. Fetal plasma cortisol increases exponentially from 120 days gestation (dGA) to term (150 dGA).However the rise in cortisol has not been shown to be accompanied by a clear parallel fetal plasma ACTH rise. Thus, mechanisms other than plasma ACTH may stimulate increased fetal adrenal activity. I have demonstrated the presence in abundance of immunoreactive CRH in splanchnic nerve fibers innervating fetal sheep adrenals. Splanchnic nerve CRH immunoreactivity increases in late gestation. Other investigators have shown that CRH directly increases neonatal adrenal blood flow and steroidogenesis. Splanchnic nerve section blunts increased fetal adrenal blood flow with no effect on basal adrenal blood flow . There are no data on CRH’s effect on fetal adrenal blood flow I have a central hypothesis to my work that says that CRH increases fetal adrenal blood flow and plasma cortisol and that the adrenal blood flow response to CRH increases in late gestation at the time of the fetal cortisol rise prior to delivery. This hypothesis addresses the potential role of a direct, gestational age related action of CRH on fetal adrenal blood flow and cortisol production that initiates delivery and the maturation of key organ systems the fetus will need to adapt to its new environment after birth.

I have worked with the fetal sheep model with bilateral hypothalamic paraventricular nuclei lesions. This model has low basal fetal plasma ACTH which does not increase following CRH injection to the fetus. Since injected CRH cannot increase pituitary ACTH driven adrenal blood flow or fetal adrenal cortisol secretion, I am conducting studies in which I give CRH to lesioned fetuses to determine the effect of CRH on fetal adrenal blood flow and plasma cortisol. I am also interested in changes in adrenal blood flow sensitivity to CRH at the time of gestation when fetal plasma cortisol shows its prepartum rise. The fetal sheep is a major in vivo animal experimental model for studies of late fetal and neonatal function.