Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells.

Published on Jun 30, 2019in Peptides2.843
· DOI :10.1016/J.PEPTIDES.2019.01.002
Satoshi Fujisawa3
Estimated H-index: 3
(Okayama University),
Motoshi Komatsubara5
Estimated H-index: 5
(Okayama University)
+ 5 AuthorsFumio Otsuka35
Estimated H-index: 35
(Okayama University)
Sources
Abstract
Abstract The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.
📖 Papers frequently viewed together
20067.52Diabetologia
9 Authors (E. Göncz, ..., U. Plockinger)
14 Citations
12 Citations
References46
Newest
#1Shiho Fujita (Okayama University)H-Index: 4
#2Toru Hasegawa (Okayama University)H-Index: 4
Last. Fumio Otsuka (Okayama University)H-Index: 35
view all 10 authors...
Abstract The involvement of orexins in reproductive function has been gradually uncovered. However, the functional role of orexins in ovarian steroidogenesis remains unclear. In the present study, we investigated the effects of orexin A on ovarian steroidogenesis by using rat primary granulosa cells that express both OX1 and OX2 receptors for orexins. Treatment with orexin A enhanced progesterone, but not estradiol, biosynthesis induced by FSH, whereas it did not affect basal levels of progester...
13 CitationsSource
#1Kanako Ogura-OchiH-Index: 5
#2Satoshi FujisawaH-Index: 3
Last. Fumio Otsuka (Okayama University)H-Index: 35
view all 9 authors...
Abstract The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT...
5 CitationsSource
#1Kishio Toma (Okayama University)H-Index: 8
#2Fumio Otsuka (Okayama University)H-Index: 35
Last. Hirofumi Makino (Okayama University)H-Index: 98
view all 8 authors...
The effects of somatostatin analogs and roles of BMP-6 in the regulation of luteinizing hormone (LH) secretion were investigated using mouse gonadotrope LβT2 cells. LH mRNA expression and LH secretion induced by GnRH were suppressed by treatments with somatostatin analogs, including octreotide and pasireotide, in LβT2 cells. Of note, the inhibitory effects of somatostatin analogs on LH secretion were enhanced by the action of BMP-6. BMP-6 increased the expression levels of somatostatin receptor ...
7 CitationsSource
#1Naoko Tsukamoto-Yamauchi (Okayama University)H-Index: 6
#2Tomohiro Terasaka (Okayama University)H-Index: 10
Last. Fumio Otsuka (Okayama University)H-Index: 35
view all 4 authors...
Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimu...
14 CitationsSource
#1Tomohiro Terasaka (Okayama University)H-Index: 10
#2Fumio Otsuka (Okayama University)H-Index: 35
Last. Hirofumi Makino (Okayama University)H-Index: 98
view all 10 authors...
Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment wi...
31 CitationsSource
#1Tian-Rui Xu (Kunming University of Science and Technology)H-Index: 12
#2Yang Yang (Kunming University of Science and Technology)H-Index: 8
Last. Ying Liu (Kunming University of Science and Technology)H-Index: 8
view all 5 authors...
The orexin peptides (orexin A, orexin B) and their receptors (orexin receptor type 1, orexin receptor type 2) are involved in multiple physiological processes such as the regulation of sleep/wakefulness state, energy homeostasis and reward seeking. A result of this has been the development of small-molecule orexin receptor antagonists as novel therapies for the treatment of insomnia and drug addiction. Increased levels of signaling via the orexin peptide/receptor system may protect against obesi...
79 CitationsSource
#1Anthony L. Gotter (USMA: United States Military Academy)H-Index: 27
#2Andrea L. Webber (USMA: United States Military Academy)H-Index: 1
Last. Christopher J. Winrow (USMA: United States Military Academy)H-Index: 29
view all 5 authors...
Orexin signaling is essential for normal regulation of arousal and behavioral state control and represents an attractive target for therapeutics combating insomnia. Alternatively termed hypocretins, these neuropeptides were named to reflect sequence similarity to incretins and their potential to promote feeding. Current nomenclature reflects these molecular and biochemical discovery approaches in which HCRT , HCRTR1 , and HCRTR2 genes encode prepro-orexin, the orexin 1 receptor (OX1) and the ore...
127 CitationsSource
#1Fumio Otsuka (Okayama University)H-Index: 35
#2Naoko Tsukamoto (Okayama University)H-Index: 13
Last. Hirofumi Makino (Okayama University)H-Index: 98
view all 5 authors...
Abstract The existence of a functional bone morphogenetic protein (BMP) system in the pituitary has been recognized. Recent studies have provided evidence that BMPs elicit differential actions in the regulation of prolactin (PRL) and adrenocorticotropin (ACTH) release in lactotropinoma and corticotropinoma cells, respectively. BMPs play a key role in the modulation of somatostatin receptor (SSTR) sensitivity of lactosomatotrope cells in an autocrine/paracrine manner. In addition, SSTR action enh...
16 CitationsSource
#1Masaya Takeda (UCSD: University of California, San Diego)H-Index: 19
#1Masaya Takeda (UCSD: University of California, San Diego)H-Index: 1
Last. Mark A. Lawson (UCSD: University of California, San Diego)H-Index: 25
view all 8 authors...
It is known that bone morphogenetic proteins (BMPs) regulate gonadotropin transcription and production by pituitary gonadotrope cells. However, the role of BMPs in gonadotropin-releasing hormone (GnRH)-induced FSH production remains uncertain. Here, we describe a functional link between BMP-6 and BMP-7 signals and FSH transcriptional activity induced by GnRH using mouse gonadotrope LβT2 cells. In LβT2 cells, BMP-6 and BMP-7 increased mouse FSHβ-promoter activity in a concentration-dependent mann...
14 CitationsSource
#1Anna Urbańska (PAN: Polish Academy of Sciences)H-Index: 5
#2Paulina Sokołowska (PAN: Polish Academy of Sciences)H-Index: 7
Last. Jolanta B. Zawilska (PAN: Polish Academy of Sciences)H-Index: 28
view all 8 authors...
Orexins A and B are newly discovered neuropeptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX1 and OX2. In this study, we examined the expression of orexin receptors and effects of the receptors’ activation on cyclic AMP formation in the primary neuronal cell cultures from rat cerebral cortex. Both types of orexin receptors were expressed in rat cortical neurons; the level of OX2R was markedly higher compared to OX1R. Orexin A (an agonist of OX1R and OX2R)...
25 CitationsSource
Cited By2
Newest
#1Satoshi Fujisawa (Okayama University)H-Index: 3
#2Motoshi Komatsubara (Okayama University)H-Index: 5
Last. Fumio Otsuka (Okayama University)H-Index: 35
view all 7 authors...
Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pit...
Source
#1Soheil Mohammadi (Tehran University of Medical Sciences)H-Index: 3
#1Soheil Mohammadi (Tehran University of Medical Sciences)H-Index: 29
Last. Nima Rezaei (Tehran University of Medical Sciences)H-Index: 80
view all 5 authors...
Abstract Narcolepsy, a sleep disorder characterized by loss of hypocretin neurons, has been associated with metabolic disturbances. Although the metabolic alterations in narcolepsy patients are widely investigated in the literature, the results are controversial. We performed a systematic search of literature to identify metabolic profiling studies in narcolepsy patients. A total of 48 studies were included in the meta-analysis. Narcolepsy patients exhibited higher prevalence of obesity (log OR=...
Source