Evidence that dehydroepiandrosterone, DHEA, directly inhibits GnRH gene expression in GT1–7 hypothalamic neurons

Cui, Hong; Lin, Shuo-Yen J.; Belsham, Denise D.

doi:10.1016/s0303-7207(03)00121-7

Cited by 15 publications

(8 citation statements)

References 54 publications

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“…For instance, in these cells, several studies reported that DHT and testosterone (1–10 nM) [9,10,27], as well as DHEA (10 −4 M), decreased GnRH transcript [28,82]. In the same line of evidence, our data showed that 17α-meT decreased intracellular GnRH expression, suggesting repressive effects on FSH and LH, hormonal changes that might represent dysregulation of the endocrine system.…”

Section: Discussionsupporting

confidence: 84%

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids

et al. 2017

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The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH). In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM). These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

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Section: Discussionsupporting

confidence: 84%

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids

et al. 2017

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“…A related consideration is that both cell type and environment influence the metabolism of DHEA. For example, in cultured GT1-7 cells and embryonic rat hippocampal neurons, 7␣-OH-DHEA and 7␤-OH-DHEA accounted for about 90% of the total metabolites, while in BV2 microglia, a higher yield of estrone, estradiol, and testosterone was observed with DHEA as substrate [29][30][31]. Adione and Adiol have been detected as metabolites in astrocytes [41], but the yield is significantly influenced by cell density [42].…”

Section: Discussionmentioning

confidence: 99%

“…An LC/MS analysis of rat liver homogenates showed that 7␣-OH-DHEA, 7␤-OH-DHEA, and 7-oxo-DHEA were the dominant metabolites, with Adione and Adiol formed later [28]. In studies of brain tissue, 7-hydroxylation was the principal pathway in both embryonic rat hypothalamus and GT1-7 cells, a hypothalamic cell line [29,30]. Investigation of additional neural cell lines showed that mouse BV2 microglia produced estradiol, estrone, and T, while other neural cells preferentially formed 7-hydroxylated metabolites [31].…”

Section: Introductionmentioning

confidence: 99%

Dehydroepiandrosterone and its metabolites: Differential effects on androgen receptor trafficking and transcriptional activity

Simon

2006

The Journal of Steroid Biochemistry and Molecular Biology

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“…In the last few years, the receptors for several families of neurotransmitters known to modify GnRH secretion have been identified on GT1 cells, and the stimulatory or inhibitory activity of the corresponding ligands on GnRH secretion has been documented [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion1

Yang

Zhou

Liu

et al. 2005

Acta Pharmacologica Sinica

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Aim: To investigate the expression of feeding‐related peptide receptors mRNA in GT1‐7 cell line and roles of leptin and orexins in the control of GnRH secretion. Methods: Receptors ofbombesin3, cholecystokinin (CCK)‐A, CCK‐B, glucagon‐like peptide (GLP)1, melanin‐concentrating hormone (MCH)1, orexin1, orexin2, neuromedin‐B, neuropeptide Y (NPY) 1 and NPY5, neurotensin (NT) 1, NT2, NT3, and leptin receptor long form mRNA in GT1‐7 cells were detected by reversed transcriptase‐polymerase chain reaction. GT1‐7 cells were treated with leptin, orexin A and orexin B at a cohort of concentrations for different lengths of time, and GnRH in medium was determined by radioimmunoassay (RIA). Results: Receptors of bombesin 3, CCK‐B, GLP1, MCH1, orexin1, neuromedin‐B, NPY1, NPY5, NT1, NT3, and leptin receptor long form mRNA were expressed in GT1‐7 cells, of which, receptors of GLP1, neuromedin‐B, NPY1, and NT3 were highly expressed. No amplified fragments of orexin2, NT2, and CCK‐A receptor cDNA were generated with GT1‐7 RNA, indicating that the GT1‐7 cells did not express mRNA of them. Leptin induced a significant stimulation of GnRH release, the results being most significant at 0.1 nmol/L for 15 min. In contrast to other studies in hypothalamic explants, neither orexin A nor orexin B affected basal GnRH secretion over a wide range of concentrations ranging from 1 nmol/L to 500 nmol/Lat 15, 30, and 60 min. Conclusion: Feeding and reproductive function are closely linked. Many orexigenic and anorexigenic signals may control feeding behavior as well as alter GnRH secretion through their receptors on GnRH neurons.

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Evidence that dehydroepiandrosterone, DHEA, directly inhibits GnRH gene expression in GT1–7 hypothalamic neurons

Cited by 15 publications

References 54 publications

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids

Dehydroepiandrosterone and its metabolites: Differential effects on androgen receptor trafficking and transcriptional activity

Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion1

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