Role of activin, follistatin, and inhibin in the regulation of Kiss-1 gene expression in hypothalamic cell models†

Abstract

Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1–expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin α subunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.

Immuno-Neutralization of Follistatin Bioactivity Enhances the Developmental Potential of Ovarian Pre-hierarchical Follicles in Yangzhou Geese

“…However, immunization against FST significantly upregulated Gnrh1 and Gnih mRNA levels from the hypothalamus. In vitro studies had shown that activin A might act at the hypothalamus in mice and activate the secretion of GnRH by modulating Kiss1 gene expression, whereas FST reduced Kiss1 gene expression and abolished activin’s effect on the Kiss1 gene [ 43 ]. More studies are needed to understand these findings in birds.…”

Roles of intracerebral activin, inhibin, and follistatin in the regulation of Kiss-1 gene expression: Studies using primary cultures of fetal rat neuronal cells

“…In our previous study using a hypothalamic Kiss-1-expressing cell model, mHypoA-55 cells, we reported that exogenous activin increased Kiss-1 expression, whereas inhibin A and follistatin decreased its expression [ 13 ]. Our present study confirmed that these gonadal factors had similar effects on Kiss-1 gene expression when we used a more physiological neuronal cell model obtained from fetal rat brain.…”

“…Considering this report, it is possible that Kiss-1 neurons from the AVPV region of the hypothalamus were absent from our primary neuronal cells, and that the phenomena observed in this study occurred only in Kiss-1 neurons in the ARC region of the hypothalamus. In this regard, we reported previously that activin, inhibin A, and follistatin stimulation do not modify Kiss-1 expression in the mHypoA-50 cell model, which originated from hypothalamic neurons in the AVPV region [ 13 ].…”

“…Using these cells, we showed that the gene expression of the inhibin α subunit and follistatin was upregulated by E2. In addition, we revealed that Kiss-1 gene expression in mHypoA-55 cells was increased by exogenous activin stimulation, while it was repressed by exogenous inhibin A or follistatin stimulation [ 13 ]. However, it remains unclear whether Kiss-1 gene expression is regulated by activin, inhibin, and follistatin and whether their expression is influenced by circulating E2 in vivo .…”

Impact of One-Week Administration of Dihydrotestosterone in Rat Anterior Pituitary Gland

“…LβT2 cells (kindly provided by Dr. P. Mellon of the University of California, San Diego, CA) and GH3 cells (CCL-82.1, American Type Culture Collection) were plated in 35-mm tissue culture dishes and incubated with high-glucose Dulbecco's modified Eagle's medium (Sigma-Aldrich Co.) containing 10% heatinactivated foetal bovine serum and 1% penicillin-streptomycin at 37 °C under a humidified atmosphere of 5% CO 2 in air. For the stimulation experiments, the medium was changed to high-glucose Dulbecco's modified Eagle's medium containing 1% heat-inactivated foetal bovine serum and 1% penicillin-streptomycin, and the cells were incubated without (control) or with the test reagents (DHT, activin A, inhibin A, and TRH) for 24 h. e concentration and stimulation times of DHT, activin A, and inhibin A were chosen because we already knew that these concentrations and stimulation times cause cultured hypothalamic cells to change their characteristics [21,22].…”