Thyrotropin Expression in Hypophyseal Pars Tuberalis-Specific Cells is 3,5,3′-Triiodothyronine, Thyrotropin-Releasing Hormone, and Pit-1 Independent*

Abstract

The expression of TSH subunit genes (TSH␣ and -␤) in pituitary thyrotropes is primarily regulated via circulating thyroid hormone levels (T 3 ) and the hypothalamic TRH. Hypophyseal pars tuberalis (PT)-specific cells also express both hormonal subunits of TSH, but do not resemble thyrotropes of the pars distalis (PD) with respect to their distinct morphology, secretion, and direct modulation of TSH expression by photoperiodic inputs and melatonin. To investigate whether this distinct regulation of TSH is related to a different molecular structure or different signaling cascades, we analyzed PT-specific TSH and its transcriptional regulation in ovine PT-specific cells. After construction of PT-and PD-specific complementary DNA (cDNA) libraries, the cloning and sequencing of several TSH␣ and -␤ subunit clones revealed identical sizes and sequences for the translated and untranslated regions in both hypophyseal compartments. Transcription start site analysis also displayed three identical start sites for the transcription of TSH␤ in PT and PD. After cloning of the ovine TRH receptor cDNA and a partial T 3 receptor cDNA, in situ hybridization, Northern blot analysis, and PCR experiments showed that TRH and T 3 receptors are not expressed in specific cells of the PT. The transcription factor Pit-1 that is involved in TSH expression of thyrotropes could only be detected in the PD.In additional experiments rats were treated with T 4 or TRH, and subsequent in situ hybridization studies showed that TSH␤ messenger RNA (mRNA) formation was not altered in the PT. In the PD, however, TSH␤ mRNA was significantly reduced in the T 4 -treated group, but was enhanced in the TRH-treated group. We conclude that PT-specific cells of the pituitary are characterized by the transcription of TSH subunits that are identical to TSH expressed in thyrotropes of the PD. The absence of TRH, T 3 receptor mRNA, and Pit-1, respectively, as well as the different reactions compared to PD thyrotropes in in vivo experiments lead to the conclusion that the expression of TSH in PT-specific cells of the pituitary is not regulated via the classical thyrotrope receptors and their intracellular pathways, but through a novel, photoperiod-dependent mechanism. (Endocrinology 138: 1019 -1028, 1997) T HE HYPOPHYSEAL glycoprotein hormone, TSH, consists of two noncovalently bound subunits, ␣ and ␤, which are encoded by separate genes on different chromosomes (1). The ␣-subunit is common to the other members of the glycoprotein hormone family, pituitary LH and FSH and placental CG, whereas the unique ␤-subunit determines the specificity of the hormonal dimer (2). The expression and secretion of TSH␣ and -␤ subunits in pituitary thyrotropes are closely regulated by hypothalamic factors released from the median eminence into the hypophyseal blood flow, in particular TRH, and a feedback control by thyroid hormones (e.g. T 3 ) (3, 4). T 3 acts as a suppressor of TSH transcription after attachment to a nuclear T 3 receptor (TR␤) that binds as a T 3 -receptor c...

Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man

“…Our results show TSHB and CGA immunoreactivity in numerous PT cells whose somata are smaller than those of the thyrotropes in the PD. A similar distribution of TSHB immunoreactivity has been observed in hamster (Yasuo et al 2010a), mice (Unfried et al 2009), and sheep (Böckers et al 1996;Bockmann et al 1997). These data support the hypothesis that TSHB is a conserved molecular messenger in the PT, and they suggest a functional role for TSHB also in man.…”

Hes1 regulates formations of the hypophyseal pars tuberalis and the hypothalamus

“…The PT cells of rats, hamsters, and mice are immunoreactive for TSHβ. However, in contrast to TSH cells of the pars distalis, the PT cells lack receptors for both thyrotropin-releasing hormone and thyroid hormone and are Pit-1 independent (Bockmann et al 1997). In the rat pars tuberalis, all MT1-positive cells are colocalized with αGSU and most with TSHβ (Klosen et al 2002).…”

Cell organization of the rat pars tuberalis. Evidence for open communication between pars tuberalis cells, cerebrospinal fluid and tanycytes

“…In all mammals studied, these cells react with antibodies against the common α-subunit of thyrotrophin (TSH) and the gonadotrophins (luteinizing hormone and follicle-stimulating hormone) (Gross 1984;Stoeckel et al 1994;Kameda et al 2000). However, PTspecific cells differ from the pars distalis (PD) gonadotrophs and thyrotrophs with respect to their morphological appearance, immunoreaction patterns and secretory activity (Bockers et al 1990;Bockmann et al 1997;Sakai et al 1999;Wittkowski et al 1999). Nevertheless, typical PD gonadotrophs and thyrotrophs are found in the ventrocaudal portion of the PT, a transition zone between PT and PD (Gross 1984).…”