Cellular Localization of Orexin Receptors in Human Pituitary

Abstract

Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and relationated with the stimulation of food intake. They act on G protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2 (OX(2)R), respectively. In the present study, we used RT-PCR and immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was carried out using histological techniques. By consecutive sections we demonstrated that OX(1)R was present in acidophil, diffusely distributed cells, which represent the half of the total adenohypophysis cell population. As was expected, these cells were shown to coexpress GH. OX(2)R was found in the pars intermedia and in clusters of basophil cells of the anterior pituitary, which coexpress ACTH. These results were confirmed by double immunofluorescence techniques. We also found focal positivity in axon terminals of neurohypophysis, more intense for OX(2)R than for OX(1)R. In conclusion, these results demonstrated for the first time that OX(1)R and OX(2)R were expressed by somatotrope and corticotrope cells, respectively.

Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons

“…In addition, OX1R expression was also detected at high level in the pituitary gonadotrope cell line, LβT2. This observation is consistent with studies in rats, human and sheep [39,40,41] supporting the potential role of orexin A in the regulation of reproductive neuroendocrine processes at the pituitary level. Furthermore, we demonstrated that orexin A likely stimulates GnRH mRNA expression and release in vivo by a direct action, using immortalized, GnRH-producing GT1-7 cells in vitro.…”

Orexin-B Augments Voltage-Gated L-Type Ca²⁺ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes

“…This hypothesis is supported by several other lines of evidence. Firstly, orexins and their receptors were recently discovered in the anterior pituitary of both the rat and human, indicating a possible paracrine and/or autocrine role of orexins in modifying somatotropes [14, 15]. Secondly, orexins induced significant changes in the electrophysiological activities of neurons and other cells [16, 17].…”

Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

“…For example, the ORX peptide/receptor system was observed in the pituitary (Date et al, 2000; Blanco et al, 2001; Silveyra et al, 2007). The relevance of ORXs in the pituitary is also highlighted by the evidence that ORX-A-like molecule and OX1R are widely present in the adenohypophysis of Xenopus (Suzuki et al, 2007; Chieffi et al, 2014), and this underlines a highly conserved function.…”

“…In the Nile tilapia ( Oreochromis niloticus , Monda et al, 2008; Suzuki et al, 2009), an ORX-B-like substance might be secreted from LH- or TSH-containing cells and might regulate the pituitary function, as well. Blanco et al (2001) detected the presence of ORX-A and ORX-B in the human adenohypophysis cell types. The ORX-A was located in 33% of pituitary cells, including PRL (82 ± 5.3%), TSH (18 ± 2.3%), growth hormone (GH; 10 ± 2.3%), Follicle-Stimulating Hormone (FSH; 8 ± 2.6%) and LH (7 ± 3.2%) cells, but not in corticotrope cells (Monda et al, 2006, 2007).…”