Regulatory effects of paraventricular nucleus injections of ghrelin on the hypothalamus-pituitary-thyroid axis via CB1 receptors in male rats

Abstract

Paraventricular nucleus (PVN) neurons play critical roles in thyrotropin-releasing hormone (TRH) synthesis and the regulation of energetic homeostasis through the hypothalamus-pituitary-thyroid (HPT) axis. Endocannabinoids induce inhibitory effects on TRH-producing neurons via the type 1 cannabinoid receptor [CB₁]. The administration of ghrelin modulates thyrotropes and decreases TSH and T4. The aim of present study was to evaluate the interactions of ghrelin on the HPT axis and CB₁ receptors in the PVN. In this experimental study, 54 male Wistar rats weighing 320–370 g were divided into 10 groups and stereotaxic surgery was performed on all animals. control group received a saline injection, while the experimental groups received one of the following injections: ghrelin (5 nm/μL), ACPA (CB₁ receptor agonist; 1.25, 2.5, or 5 ng/μL), AM251 (CB₁ receptor antagonist; 50, 100, or 200 ng/μL), ACPA + ghrelin (5 ng/μL + 5 ng/μL) and AM251 + ghrelin (200 ng/μL + 5 nm/μL) into the PVN once a day for 3 days. Serum TSH, T₃, T₄, and T₃ uptake levels were evaluated by radioimmunoassay, and FT₄I and FT₃I were calculated. The present study showed that PVN injections of ACPA and ghrelin alone inhibited thyroid gland secretion, and AM251 stimulated this secretion. ACPA and AM251 increased TSH levels, while ghrelin decreased these levels. The coadministration of ACPA with ghrelin increased TSH levels, but AM251 with ghrelin enhanced serum FT₄I. Lastly, injections of ACPA and ACPA with ghrelin decreased thyroid hormones and increased TSH levels. Central injections of ghrelin modulate the HPT axis via the CB₁ receptor. ACPA, ghrelin, and ACPA with ghrelin play inhibitory roles in the regulation of thyroid hormones in the PVN, while AM251 was able to stimulate thyroid hormone secretion.