Abstract
Olfactory marker protein (OMP) is a marker of olfactory receptor-mediated chemoreception, even outside the olfactory system. Here, we report that OMP expression in the pituitary gland plays a role in basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) production and secretion. We found that OMP was expressed in human and rodent pituitary glands, especially in PRL-secreting lactotrophs. OMP knockdown in GH4 rat pituitary cells increased PRL production and secretion via extracellular signal-regulated kinase (ERK)1/2 signaling. Real-time PCR analysis and the Ca2+ influx assay revealed that OMP was critical for TRH-induced PRL secretion. OMP-knockout mice showed lower fertility than control mice, which was associated with increased basal PRL production via activation of ERK1/2 signaling and reduced TRH-induced PRL secretion. However, both in vitro and in vivo results indicated that OMP was only required for hormone production and secretion because ERK1/2 activation failed to stimulate cell proliferation. Additionally, patients with prolactinoma lacked OMP expression in tumor tissues with hyperactivated ERK1/2 signaling. These findings indicate that OMP plays a role in PRL production and secretion in lactotrophs through the modulation of Ca2+ and TRH signaling.
Highlights
Prolactin (PRL) is a hormone that is mainly secreted by lactotrophs of the anterior pituitary gland and is involved in many biological processes, including reproduction and lactation[1]
Olfactory marker protein (OMP) expression in rat pituitary cell lines and tissue To determine whether OMP is expressed in the anterior pituitary gland, we carried out an immunohistochemical analysis using antibodies against various hormones, including PRL, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH) produced by somatotrophs, lactotrophs, adrenocorticotrophs, thyrotrophs, and gonadotrophs, respectively, of the human pituitary gland
A portion of cells positive for TSH, FSH, GH, and ACTH was negative for OMP (Fig. 1a and S1 Fig)
Summary
Prolactin (PRL) is a hormone that is mainly secreted by lactotrophs of the anterior pituitary gland and is involved in many biological processes, including reproduction and lactation[1]. Dopamine, secreted by hypothalamic neurons, is the major inhibitor of pituitary PRL secretion[3], which is induced by thyrotropin-releasing hormone (TRH) and estrogen (E2). Previous studies have shown that OMP modulates olfactory signal transduction in part by participating in Ca2+ clearance[8,9,10,11,12,13]. Microarray and RNA sequencing analyses have revealed that OMP is expressed in non-olfactory tissues, often with odorant receptors (ORs), which constitute a major class of G
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