Effects of Hormones Targeting Nuclear Receptors on Transcriptional Regulation of the Growth Hormone Gene in the MtT/S Rat Somatotrope Cell Line

Abstract

We have examined the effects of nuclear receptor hormones such as glucocorticoid, gonadal steroid hormones, thyroid hormone and retinoids on the transcriptional regulation of the 5′-promoter activity of growth hormone (GH) gene using the MtT/S rat pure somatotrope cell line or MtT/SGL, a subclone of MtT/S in which the rat GH gene 5′-promoter (1.7 Kb)-luciferase fusion gene was stably incorporated. RT-PCR analyses revealed that receptors for all the hormones except androgen receptor were expressed in the cell line. Triiodothyronine (T₃, 10 nM) transiently but significantly stimulated the promoter activity of GH gene, whereas retinoic acids (9-cis and all-trans, both 1 µM) showed sustained stimulation. There were no additive effects among the T₃, all-trans, and9-cis retinoic acids. Synthetic glucocorticoid hormone dexamethasone (100 nM) showed an inhibitory effect but, interestingly, significantly enhanced T₃-stimulated GH promoter activity during long-term incubation. Among the gonadal steroid hormones tested, estradiol and estriol had significant stimulatory effects, and deletion analysis showed that the estrogen effect was maintained with the shortest construct examined (–150 to +6, +1 denotes the transcription start site). These results suggest that thyroid hormone and retinoids stimulate the transcription of GH gene, probably through a common response element, whereas glucocorticoid has both negative and positive effects on GH expression, depending on the combination with other hormones and the time of exposure. Estrogens also have direct stimulatory effects through the proximal promoter region of GH gene.

Identification of Igf2, Igfbp2 and Enpp2 as Estrogen-Responsive Genes in Rat Hippocampus

“…Rat pituitary tumor cell lines, GH3 and MtT/S, were obtained from Health Science Research Resources Bank and Riken BioResource Center, respectively [12,13]. Cells were maintained in a half and half mixture of Dulbecco's modified Eagle's medium (DMEM) and F-12 medium supplemented with 2.5% fetal bovine serum (FBS) and 10% horse serum at 37°C in 5% CO 2 and a humidified atmosphere.…”

Examination of the direct effects of metabolic factors on somatotrope function in a non-human primate model, Papio anubis

“…Glucocorticoids modestly stimulate the activity of the hGH gene promoter, where this effect has been isolated to an atypical glucocorticoid response element (GRE) located in the first intron (Slater et al 1985, Brent et al 1988. In contrast, the rGH gene promoter lacks consensus GREs and is unresponsive to glucocorticoid stimulation, and in some reports, promoter activity is actually inhibited by glucocorticoid treatment (Brent et al 1988, Strobl et al 1989, Iwasaki et al 2003. However, glucocorticoids have also been shown to enhance rat GH mRNA levels by stabilizing the transcript (Paek & Axel 1987).…”

“…However, glucocorticoids have also been shown to enhance rat GH mRNA levels by stabilizing the transcript (Paek & Axel 1987). In addition, glucocorticoids work synergistically with thyroid hormone to enhance the expression of both the rat and human GH transcripts (Evans et al 1982, Spindler et al 1982, Martinoli et al 1991, Iwasaki et al 2003.…”

Avaliação da estatura final e mineralização óssea de pacientes adultos portadores de síndrome nefrótica idiopática na infância e adolescência

“…Os hormônios tireoideos agem, tanto na hipófise quanto no hipotálamo, estimulando a transcrição dos genes promotores de GH, assim como a produção e secreção deste hormônio (Argente,1994;Iwasaki, 2004;Norris, 2003). Por outro lado, os hormônios tireoideos também estimulam diretamente na adenohipófise a expressão dos genes dos receptores da somatostatina (Lam,1999 (Argente, 1994;Bondanelli, 2008).…”

“…O estrogênio influencia a expressão do gene do IGF-I estimulando a expressão de seu mRNA no útero mas inibe esta transcrição estimulada pelo GH no fígado (Rajkumar, 1996), e os hormônios tireóideos participam desta regulação aumentando a ligação hepática do GH e conseqüentemente a síntese de IGF-1 (Iwasaki, 2004;Norris, 2003).…”