scholarly journals Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis

2012 ◽  
Vol 212 (3) ◽  
pp. 383-394 ◽  
Author(s):  
Sayaka Aizawa ◽  
Takafumi Sakai ◽  
Ichiro Sakata

Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression ofTSHβandαGSUin PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism forTSHβexpression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of theKA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well asGLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid onTSHβexpression andαGSUexpression in PT slice cultures.l-Glutamine andl-glutamic acid significantly stimulatedTSHβexpression in PT slices after 2- and 4-h treatments, and the effect ofl-glutamic acid was stronger than that ofl-glutamine. In contrast, treatment with glutamine and glutamic acid did not affectαGSUexpression in the PT or the expression ofTSHβorαGSUin the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls inducesTSHβexpression via the KA2 in an autocrine and/or paracrine manner in the PT.

2007 ◽  
Vol 19 (11) ◽  
pp. 839-846 ◽  
Author(s):  
S. Aizawa ◽  
S. Hoshino ◽  
I. Sakata ◽  
A. Adachi ◽  
S. Yashima ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Leonard Cheung ◽  
Alexandre Daly ◽  
Michelle Brinkmeier ◽  
Sally Ann Camper

Abstract We implemented single-cell RNA sequencing (scRNAseq) technology as a discovery tool to identify factors enriched in differentiated thyrotropes. Thyroid-stimulating hormone (TSH) is produced in the pars distalis of the anterior pituitary (AP) and primarily acts on the thyroid gland to regulate metabolism through T3/T4. However, TSH is also produced by cells in the pars tuberalis (PT), which is comprised of a thin layer of cells that extends rostrally from the pars distalis along the pituitary stalk to the median eminence in the hypothalamus. TSH produced by PT thyrotropes acts on hypothalamic tanycytes to regulate seasonal reproduction. PT thyrotropes likely descend from rostral tip thyrotropes that arise at e12.5 of mouse development, which transcribe the TSH beta subunit (Tshb) without detectable expression of the transcription factor POU1F1. POU1F1 is required for Tshb transcription in thyrotropes of the adenohypophysis, and it acts synergistically with GATA2 to drive cell fate. The molecular mechanisms driving Tshb expression independently of Pou1f1 in PT thyrotropes are unclear. Thyrotropes are the least abundant endocrine cell-type in the pituitary gland. We used genetic labeling and fluorescence-activated cell sorting (FACS) to enrich for thyrotropes for single-cell sequencing. We performed scRNAseq on 7-day-old GFP-positive pituitary cells from Tshb-Cre; R26-LSL-eYFP and intact whole pituitaries, recovering more than 15,000 cells altogether. We observe two distinct populations of cells expressing Tshb. The larger thyrotrope population has approximately twenty fold higher levels of Tshb and five fold higher Cga transcripts than the smaller population, and they are also distinguished by expression of Pou1f1, TSH-releasing hormone receptor (Trhr), and deiodinase 2 (Dio2), consistent with expectations for AP thyrotropes. The smaller thyrotrope population does not express Pou1f1, but those cells are characterized by expression of TSH receptor (Tshr) and melatonin receptor 1A (Mtnr1a), consistent with expectations for PT thyrotropes. They express mildly increased levels of Eya3 and Six1, although these genes are expressed in other cell-types including AP thyrotropes, stem cells, and gonadotropes. They have two-fold higher levels of Gata2 transcripts and uniquely express the transcription factor Sox14. SOX14 is a SoxB2 family transcription factor that counteracts the transcriptional activity of SoxB1 family members, such as Sox2. In conclusion, our scRNAseq has identified novel markers of PT thyrotropes and unveils novel insights into the similarities and differences in the development and function of pituitary thyrotrope subpopulations.


2021 ◽  
Vol 17 (1) ◽  
pp. 189-195
Author(s):  
Sibel Ertek

Thyrotropin (TSH) is classically known to be regulated by negative feedback from thyroid hormones and stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. At the end of the 1990s, studies showed that thyrotroph cells from the pars tuberalis (PT) did not have TRH receptors and their TSH regulation was independent from TRH stimulation. Instead, PT-thyrotroph cells were shown to have melatonin-1 (MT-1) receptors and melatonin secretion from the pineal gland stimulates TSH- subunit formation in PT. Electron microscopy examinations also revealed some important differences between PT and pars distalis (PD) thyrotrophs. PT-TSH also have low bioactivity in the peripheral circulation. Studies showed that they have different glycosylations and PT-TSH forms macro-TSH complexes in the periphery and has a longer half-life. Photoperiodism affects LH levels in animals via decreased melatonin causing increased TSH- subunit expression and induction of deiodinase-2 (DIO-2) in the brain. Mammals need a light stimulus carried into the suprachiasmatic nucleus (which is a circadian clock) and then transferred to the pineal gland to synthesize melatonin, but birds have deep brain receptors and they are stimulated directly by light stimuli to have increased PT-TSH, without the need for melatonin. Photoperiodic regulations via TSH and DIO 2/3 also have a role in appetite, seasonal immune regulation, food intake and nest-making behaviour in animals. Since humans have no clear seasonal breeding period, such studies as recent ‘’domestication locus’’ studies in poultry are interesting. PT-TSH that works like a neurotransmitter in the brain may become an important target for future studies about humans.


2018 ◽  
Vol 58 (2) ◽  
pp. 80-3
Author(s):  
Nur Rochmah ◽  
Muhammad Faizi

Background Children with type 1 diabetes mellitus (T1DM) are at risk of thyroid dysfunction. An association between diabetes duration and thyroid stimulating hormone level remains inconclusive.Objective To assess for a possible association between diabetes duration and thyroid stimulating hormone levels in children with T1DM.Methods We conducted a cross-sectional study from January to June 2017 in the Pediatric Endocrine Outpatient Clinic at Dr. Soetomo Hospital. Subjects were children with T1DM aged 7 to <18 years. Exclusion criteria were children with diabetic ketoacidosis, previously diagnosed thyroid problems, and hospitalization in the pediatric intensive care unit (PICU). Results From the 55 regular patients in our outpatient clinic, 34 patients were included in the study. Nineteen (54.3%) subjects were male, and the overall mean age was 11.3 years. Subjects’ mean duration of diabetes was 3 years and their mean thyroid stimulating hormone concentration was 3.76mIU/L. Pearson’s correlation test revealed no significant association between duration of diabetes and thyroid stimulating hormone level (rs=-0.068; P=0.703).Conclusion There is no significant association between duration of diabetes and thyroid stimulating hormone levels in children with T1DM. 


1994 ◽  
Vol 131 (3) ◽  
pp. 323-329 ◽  
Author(s):  
Antti Kaipia ◽  
Tarja-Leena Penttilä ◽  
Jorma Toppari

Kaipia A, Penttilä T-L, ToppariJ. Follicle-stimulating hormone regulation of inhibin α-subunit mRNA in staged rat seminiferous tubules. Eur J Endocrinol 1994;131:323–9. ISSN 0804–4643 Steady-state levels of inhibin-α and -βB mRNAs are higher in stages II–VI of the seminiferous epithelial cycle than in stages VII–VIII We investigated follicle-stimulating hormone (FSH) regulation of inhibin α-subunit mRNA in stages II–VI and VII–VIII to study whether the stage specificity is due to differential hormonal regulation by FSH. Follicle-stimulating hormone caused a significant increase of inhibin-α mRNA levels in both stages during a 20-h incubation. The mechanism of the FSH effect was studied further in stages VII-VIII. Maximal stimulation of the inhibin-α mRNA level was achieved with 100 μg/l FSH, dibutyryl-3′,5′-cyclic adenosine monophosphate (db-cAMP, 0.2 mmol/l) and Spadenosine-3′,5′-monophosphothionate (Sp-cAMPS, 10 μmol/l) (a cAMP agonist). The presence of RpcAMPS (200 μmol/l) (a cAMP antagonist) abolished the stimulation, Rp-cAMPS alone had no effect. inhibin-βB mRNA levels in stages VII–VIII were not affected by FSH, db-cAMP, Sp-cAMPS or Rp-cAMPS. Phorbol 12-myristate 13-acetate (100 nmol/l) had no effect on inhibin-α or -βB mRNA levels. Actinomycin D abolished the stimulatory effect of FSH on inhibin-α mRNA expression. In conclusion, FSH stimulated inhibin-α mRNA expression similarly both in stages II–VI and VII–VIII of the seminiferous epithelial cycle and the stimulation in stages VII–VIII was cAMP-mediated. Jorma Toppari, University of Turku, Institute of Biomedicine, Department of Physiology, Kiinamyllynkatu 10, FIN-20520 Turku, Finland


2016 ◽  
Vol 229 (3) ◽  
pp. R117-R127 ◽  
Author(s):  
Taeko Nishiwaki-Ohkawa ◽  
Takashi Yoshimura

Animals that inhabit mid- to high-latitude regions exhibit various adaptive behaviors, such as migration, reproduction, molting and hibernation in response to seasonal cues. These adaptive behaviors are tightly regulated by seasonal changes in photoperiod, the relative day length vs night length. Recently, the regulatory pathway of seasonal reproduction has been elucidated using quail. In birds, deep brain photoreceptors receive and transmit light information to the pars tuberalis in the pituitary gland, which induces the secretion of thyroid-stimulating hormone. Thyroid-stimulating hormone locally activates thyroid hormone via induction of type 2 deiodinase in the mediobasal hypothalamus. Thyroid hormone then induces morphological changes in the terminals of neurons that express gonadotropin-releasing hormone and facilitates gonadotropin secretion from the pituitary gland. In mammals, light information is received by photoreceptors in the retina and neurally transmitted to the pineal gland, where it inhibits the synthesis and secretion of melatonin, which is crucial for seasonal reproduction. Importantly, the signaling pathway downstream of light detection and signaling is fully conserved between mammals and birds. In fish, the regulatory components of seasonal reproduction are integrated, from light detection to neuroendocrine output, in a fish-specific organ called the saccus vasculosus. Various physiological processes in humans are also influenced by seasonal environmental changes. The findings discussed herein may provide clues to addressing human diseases, such as seasonal affective disorder.


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