The Actions of Tuberoinfundibular Peptide on the Hypothalamo-Pituitary Axes

Abstract

Tuberoinfundibular peptide is a recently discovered agonist for the PTH receptor-2; the latter has a wide distribution including the external zone of the median eminence of the hypothalamus, suggesting a role in neuroendocrine function. We have investigated the effects of tuberoinfundibular peptide on the hypothalamo-pituitary axes in vitro and in vivo. Tuberoinfundibular peptide had effects on the hypothalamo-pituitary-adrenal axis with increased release of ACTH-releasing factor (tuberoinfundibular peptide 100 nm 4.4 ± 0.6 pmol/explant vs. control 2.9 ± 0.4 pmol/explant, P < 0.001) and increased release of arginine vasopressin (tuberoinfundibular peptide 100 nm 563.5 ± 55.5 fmol/explant vs. control 73.4 ± 9.6 fmol/explant, P < 0.01) from in vitro hypothalamic explants. Intracerebroventricular administration of tuberoinfundibular peptide and PTH(1–34) resulted in elevated plasma ACTH at 10 min post injection (saline 13.5 ± 2.1 pg/ml, tuberoinfundibular peptide 3 nmol 32.3 ± 4.0 pg/ml; P < 0.01 to saline: PTH(1–34) 10 nmol 28.9 ± 3.2 pg/ml: P < 0.05 to saline). Tuberoinfundibular peptide also had both in vitro and in vivo effects on the hypothalamo-pituitary-gonadal axis with increased release of LH-releasing hormone (tuberoinfundibular peptide 100 nm 28.5 ± 5.1 fmol/explant vs. control 19.3 ± 2.5 fmol/explant, P < 0.05) from in vitro hypothalamic explants. Both intracerebroventricular and peripheral administration of tuberoinfundibular peptide had effects on the hypothalamo-pituitary-gonadal axis. Intracerebroventricular injection of tuberoinfundibular peptide increased plasma LH (tuberoinfundibular peptide 10 nmol 0.70 ± 0.09 ng/ml vs. saline 0.42 ± 0.04 ng/ml at 10 min, P < 0.05). Intraperitoneal administration of tuberoinfundibular peptide also increased plasma LH (tuberoinfundibular peptide 30 nmol 0.53 ± 0.09 ng/ml vs. saline 0.21 ± 0.04 ng/ml at 10 min, P < 0.05). In addition to these actions on the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes, an increased release of GH-releasing factor (GRF) from hypothalamic explants (tuberoinfundibular peptide 100 nm 770.9 ± 90.7 pg/explant vs. control 657.8 ± 77.7 pg/explant, P < 0.01) was observed. Overall, these data show the actions of tuberoinfundibular peptide on the hypothalamo-pituitary axes and suggest that it may play a role in the control of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes.