Adrenocorticotrophin and Luteinizing Hormone Responses to N-Methyl-D-Aspartate During Fetal Development in Sheep

• Published in: Journal of neuroendocrinology 1996-04, Vol.8 (4), p.315-321
• Main Authors: Brooks, A. N., Howe, D. C.
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - analogs & derivatives; 2-Amino-5-phosphonovalerate - pharmacology; ACTH; Adrenocorticotropic Hormone - secretion; Animals; Embryonic and Fetal Development; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; fetal; Gestational Age; Luteinizing Hormone - secretion; N-Methylaspartate - pharmacology; NMDA; ontogeny; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - embryology; Pituitary Gland, Anterior - secretion; Sheep
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1046/j.1365-2826.1996.04639.x

The hypothalamic mechanisms which underlie the development of the fetal neuroendocrine system are unclear. However, in adult animals neuroactive amino‐acids, particularly those acting at the N‐methyl‐D‐aspartate (NMDA) receptor, have been shown to be important transmitters involved in the neuroendocrine regulation of the anterior pituitary gland. In this study we have investigated the potential role of NMDA in the neuroendocrine regulation of fetal pituitary function, by examining the ontogeny of LH and ACTH responses to NMDA during fetal development in sheep. Catheterized fetal sheep were injected with 3 intravenous doses of NMDA (1, 2 and 4 mg/kg; estimated fetal body weight) and saline vehicle on consecutive days between days 110–115, 120–125 and 135–140 gestation (term=145 days). At each gestational age fetuses also received a pituitary challenge test consisting of CRF (0.4 μg/kg), AVP (80 ng/kg) and GnRH (125 ng/kg). NMDA caused a significant dose‐related increase in ACTH at day 120–125 (P