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      Expression of Tuberalin II, α-Subunit of Glycoprotein Hormones and β-Thyrotropin Hormone in the Pars Tuberalis of the Rat: Immunocytochemical Evidence for Pars Tuberalis-Specific Cell Types

      review-article
      ,
      Neuroendocrinology
      S. Karger AG
      Immunocytochemistry, Pars tuberalis, Tuberalin, Ontogenesis

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          Abstract

          Increasing evidence suggests that the hypophyseal pars tuberalis (PT) plays a key role in the transduction of light/dark (melatonin) information to the endocrine system. It has been shown that PT-specific cells express melatonin receptors and thyrotropin hormone (TSH) subunits. However, these cells do not resemble thyrotrophs or any other of the pars distalis (PD) cells. There is evidence that PT-specific cells secrete a glycoprotein hormone designated as ‘tuberalin’. We have identified a putative tuberalin of 21 kDa (tuberalin II) and have raised antibodies against it. To further investigate whether tuberalin II is a distinct secretory compound of the PT, absorption studies of antituberalin II with TSH or with an extract of the rat PD containing β-TSH, β-luteinizing hormone (LH) and the common α-subunit of glycoprotein hormones (GSU), were performed. Neither of the absorption tests abolished the immunoreactivity of the PT to antituberalin II, suggesting that tuberalin II is different from TSH or the other PD glycoprotein hormones. Double immunofluorescence analyses using antibodies against tuberalin II, β-TSH and GSU revealed that in the developing and adult PT there are 3 populations of PT-specific cells expressing tuberalin II and GSU (type 1), β-TSH and GSU (type 2) and tuberalin II, β-TSH and GSU (type 3). This further indicates that tuberalin II and β-TSH correspond to different compounds and that they may be expressed either by different cells types or coexpressed in a 3rd cell type. The distribution and temporal expression of tuberalin II, β-TSH, β-LH and GSU were investigated in the developing pituitary gland. At E14.5, tuberalin II and GSU were expressed by cells of the PT primordium but not by the PD and pars intermedia primordia. The onset of expression of β-TSH, β-LH and GSU in cells of the PD occurred about 1 day later, further indicating the distinct nature of tuberalin II and supporting the earlier view that the secretion of polypeptides from the fetal rat pituitary gland begins in PT-specific cells.

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          Most cited references36

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          Thyrotrophin in the pars tuberalis triggers photoperiodic response.

          Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.
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            Ancestral TSH mechanism signals summer in a photoperiodic mammal.

            In mammals, day-length-sensitive (photoperiodic) seasonal breeding cycles depend on the pineal hormone melatonin, which modulates secretion of reproductive hormones by the anterior pituitary gland [1]. It is thought that melatonin acts in the hypothalamus to control reproduction through the release of neurosecretory signals into the pituitary portal blood supply, where they act on pituitary endocrine cells [2]. Contrastingly, we show here that during the reproductive response of Soay sheep exposed to summer day lengths, the reverse applies: Melatonin acts directly on anterior-pituitary cells, and these then relay the photoperiodic message back into the hypothalamus to control neuroendocrine output. The switch to long days causes melatonin-responsive cells in the pars tuberalis (PT) of the anterior pituitary to increase production of thyrotrophin (TSH). This acts locally on TSH-receptor-expressing cells in the adjacent mediobasal hypothalamus, leading to increased expression of type II thyroid hormone deiodinase (DIO2). DIO2 initiates the summer response by increasing hypothalamic tri-iodothyronine (T3) levels. These data and recent findings in quail [3] indicate that the TSH-expressing cells of the PT play an ancestral role in seasonal reproductive control in vertebrates. In mammals this provides the missing link between the pineal melatonin signal and thyroid-dependent seasonal biology.
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              RIGUI, a putative mammalian ortholog of the Drosophila period gene.

              The molecular components of mammalian circadian clocks are elusive. We have isolated a human gene termed RIGUI that encodes a bHLH/PAS protein 44% homologous to Drosophila period. The highly conserved mouse homolog (m-rigui) is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN), the master regulator of circadian clocks in mammals. Circadian expression in the SCN continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of m-rigui expression in the SCN. m-rigui transcripts also appear in a periodic pattern in Purkinje neurons, pars tuberalis, and retina, but with a timing of oscillation different from that seen in the SCN. Sequence homology and circadian patterns of expression suggest that RIGUI is a mammalian ortholog of the Drosophila period gene, raising the possibility that a regulator of circadian clocks is conserved.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2009
                October 2009
                15 October 2009
                : 90
                : 3
                : 269-282
                Affiliations
                Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile
                Article
                244373 Neuroendocrinology 2009;90:269–282
                10.1159/000244373
                19829005
                ce646ddb-f448-4892-bd42-3631375e3679
                © 2009 S. Karger AG, Basel

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                History
                : 08 November 2007
                : 30 December 2008
                Page count
                Figures: 6, Tables: 1, References: 48, Pages: 14
                Categories
                Chronobiology

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Pars tuberalis,Immunocytochemistry,Ontogenesis,Tuberalin

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