제1저자 강찬우(내과학교실, BK21)
교신저자 구철룡 이은직(내과학교실)
Exp Mol Med. 2018 Apr 6(4):15. doi: 10.1038/s12276-018-0035-z.
Olfactory marker protein regulates prolactin secretion and production by modulating Ca2+ and TRH signaling in lactotrophs.
Kang CW1,2, Han YE1,2, Lee MK3, Cho YH2, Kang N4, Koo J4, Ku CR5, Lee EJ6,7.
1Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.2Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea.3Department of Pathology, NHIS Ilsan Hospital, 100 Ilsan-ro Ilsan-donggu, Goyang-si, Gyeonggi-do, 10444, Korea.4Department of New Biology, DGIST, Daegu, 42988, Korea.5Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea. CR079@yuhs.ac.6Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea. EJLEE423@yuhs.ac.7Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea. EJLEE423@yuhs.ac.
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.