Liver receptor homologue-1 regulates gonadotrope function

Zheng, Weiming; Yang, Jingying; Jiang, Qiaorong; He, Zhibin; Halvorson, Lisa M.

doi:10.1677/jme-06-0001

Cited by 16 publications

(9 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the pituitary, both LRH1 and SF-1 regulate the expression of the gonadotropins (32,33,34) and of the GnRH receptor (32,35). Mice with pituitary-specific disruption of SF-1 have markedly diminished levels of pituitary gonadotropins modeling hypogonadotropic hypogonadism (36).…”

Section: Discussionmentioning

confidence: 99%

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

Kotan¹,

Cooper²,

Darcan³

et al. 2016

Jcrpe

View full text Add to dashboard Cite

Objective: What initiates the pubertal process in humans and other mammals is still unknown. We hypothesized that gene(s) taking roles in triggering human puberty may be identified by studying a cohort of idiopathic hypogonadotropic hypogonadism (IHH).Methods: A cohort of IHH cases was studied based on autozygosity mapping coupled with whole exome sequencing.Results: Our studies revealed three independent families in which IHH/delayed puberty is associated with inactivating SRA1 variants. SRA1 was the first gene to be identified to function through its protein as well as noncoding functional ribonucleic acid products. These products act as co-regulators of nuclear receptors including sex steroid receptors as well as SF-1 and LRH-1, the master regulators of steroidogenesis. Functional studies with a mutant SRA1 construct showed a reduced co-activation of ligand-dependent activity of the estrogen receptor alpha, as assessed by luciferase reporter assay in HeLa cells.Conclusion: Our findings strongly suggest that SRA1 gene function is required for initiation of puberty in humans. Furthermore, SRA1 with its alternative products and functionality may provide a potential explanation for the versatility and complexity of the pubertal process.

show abstract

Section: Discussionmentioning

confidence: 99%

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

Kotan¹,

Cooper²,

Darcan³

et al. 2016

Jcrpe

View full text Add to dashboard Cite

show abstract

“…We also studied the effects of GnRH-ANT and GnRH-A on steroidogenic factor 1 (SF-1) and liver receptor homologue-1 (LRH-1), which are transcriptional regulators of steroidogenesis and folliculogenesis (35)(36)(37)(38)(39). We have hypothesized that GnRH-ANT directly influences AMH and CYP19 II a mRNA expression, and that these effects may be mediated through transcriptional factors SF-1 and LRH-1.…”

mentioning

confidence: 99%

Gonadotropin releasing hormone antagonists suppress aromatase and anti-Müllerian hormone expression in human granulosa cells

Winkler

Bükülmez

Hardy

et al. 2010

Fertility and Sterility

View full text Add to dashboard Cite

“…Nr5a2 mRNA and protein have been identified in the anterior pituitary gland. Our laboratory has demonstrated that NR5A2 upregulates gonadotropin gene expression, acting via the previously described NR5A1 DNA-regulatory regions [28]. Furthermore, we have preliminary data that LRH-1 gene expression is stimulated by GnRH (data not shown).…”

Section: Introductionmentioning

confidence: 57%

Anterior Pituitary Gene Expression with Reproductive Aging in the Female Rat1

Zheng

Jimenez-Liñan

Rubin

et al. 2007

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary-ovarian axis undergoes functional changes with time. The aim of this study was to characterize age-related changes in pituitary gene expression for factors with known importance for gonadotroph function, including 1) steroid hormone receptors (Esr and Pgr), 2) orphan nuclear receptors [Nr5a1 (steroidogenic factor-1) and Nr5a2 (liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, inhibin, and follistatin), as well as 4) gonadotropin subunits and 5) GnRH receptors. We chose to utilize a middle-aged rat model for these studies. Young (Y; 3-mo-old) and middle-aged (MA; 9- to 12-mo-old) rats were ovariectomized, primed with estradiol, and injected with progesterone to induce an LH surge. The mRNA levels for the gonadotropin subunits and GnRH receptors were decreased in middle-aged females relative to young animals. Nr5a1 and follistatin mRNA levels were significantly greater in Y versus MA animals following ovariectomy. Furthermore, steroid-induced regulation of these genes was lost in the MA animals. Regulation of the Nr5a2, Inhba, and Inhbb transcripts was also limited to the young animals. In contrast, there were no significant differences in the mRNA levels of Esr or Pgr family members between age groups at any time point. Although this in vivo model normalizes ovarian steroid levels, it does not control for potential differences in GnRH stimulation with aging. Therefore, in a second set of experiments, we used an in vitro perifusion system to compare the effects of pulsatile GnRH in the two age groups. Nr5a1 mRNA expression was greater in Y than MA animals and was significantly decreased by GnRH pulses in both age groups. Follistatin mRNA levels increased significantly with GnRH treatment in Y animals but were not significantly changed in the MA females. Taken together, these data demonstrate gene-specific blunting of pituitary gene expression postovariectomy and during the steroid-induced surge in middle-aged rats. We propose that age-related changes in pituitary physiology may contribute to reproductive senescence.

show abstract

Liver receptor homologue-1 regulates gonadotrope function

Cited by 16 publications

References 50 publications

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

Gonadotropin releasing hormone antagonists suppress aromatase and anti-Müllerian hormone expression in human granulosa cells

Anterior Pituitary Gene Expression with Reproductive Aging in the Female Rat1

Contact Info

Product

Resources

About