Paracrine regulation of theca androgen production by granulosa cells in the ovary

Hoang, Yvonne D.; McTavish, Kirsten J.; Chang, R. Jeffrey; Shimasaki, Shunichi

doi:10.1016/j.fertnstert.2013.04.016

Cited by 21 publications

(13 citation statements)

References 43 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cyp11a1 expression in the theca cells is regulated not only by LH [23], but also by growth factors produced in granulosa cells [24]. Therefore, the decreased Cyp11a1 mRNA expression in theca cells may result from a disorder of LH secretion induced by Runx3 deletion, and/or alterations in granulosa cell functions relating to the control of theca cell functions.…”

Section: Discussionmentioning

confidence: 99%

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Ojima

Saito

Tsuchiya

et al. 2016

Journal of Reproduction and Development

View full text Add to dashboard Cite

We previously demonstrated that the Runx3 transcription factor is expressed in the hypothalami, pituitaries, and ovaries of mice, and that Runx3 knockout (Runx3−/−) mice are anovulatory and their uteri are atrophic. Runx3 mRNA expression was detected in the granulosa cells of ovarian follicles, and in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). In the present study, we examined the effects of Runx3 knockout on the gene expression of enzymes associated with steroidogenesis. We found decreased Cyp11a1 mRNA expression in Runx3−/− mouse ovaries compared with that in wild-type (wt) mouse ovaries at the age of 8 weeks. In situ hybridization analysis showed that the percentages of Cyp11a1 mRNA-expressing theca cells in follicles of Runx3−/− mice were decreased compared with those of wt mice. In accord with the alterations in Runx3−/− mouse ovaries, Kiss1 mRNA levels in ARC were increased, whereas mRNA levels of kisspeptin in AVPV were decreased, and gonadotropin-releasing hormone in the preoptic area and follicle-stimulating hormone β subunit gene were increased in Runx3−/− mice. Following an ovarian transplantation experiment between Runx3−/− mice and wt mice, corpora lutea were observed when ovaries from Runx3−/− mice were transplanted into wt mice, but not when those from wt mice were transplanted into Runx3−/− mice, suggesting that Runx3 in the hypothalamo-pituitary system may drive gonadotropin release to induce ovulation in the ovary. These findings indicate that Runx3 plays a crucial role in the hypothalamo-pituitary-gonadal axis.

show abstract

Section: Discussionmentioning

confidence: 99%

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Ojima

Saito

Tsuchiya

et al. 2016

Journal of Reproduction and Development

View full text Add to dashboard Cite

show abstract

“…Cyp11a1 expression in theca cells is regulated by LH (Magoffin and Weitsman 1993), and by growth factors and hormones produced in granulosa cells. Inhibin and activin, both produced in granulosa cells, stimulate and inhibit androgen synthesis in theca cells, respectively (Hillier 1991;Hillier et al 1991;Knight et al 2012;Hoang et al 2013). Cyp19a1 mRNA expression in granulosa cells was shown to be regulated by FSH.…”

Section: Discussionmentioning

confidence: 96%

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

et al. 2018

View full text Add to dashboard Cite

We previously demonstrated that female Runx3 knockout (Runx3 −/−) mice were anovulatory and their uteri were atrophic, and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examined the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3 −/− mouse ovaries, the numbers of primary and antral follicles were lower than those in wild type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba, and Inhbb) was also decreased in ovaries from the Runx3 −/− mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3 −/− mice than those in wt mice. Follicle stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3 −/− granulosa cells in culture, but the mRNA level in Runx3 −/− granulosa cells was lower than in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and Luteinizing hormone (LH)β subunit mRNA levels were decreased in Runx3 −/− mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells.

show abstract

“…Alternatively, granulosa cells developed under FSH may produce paracrine factors that upregulate CYP17a1 expression in the theca. In fact, exposure of immature rat ovaries in vivo or granulosa-theca cells co-cultures in vitro to FSH for 24 h results in marked increases in ovarian or thecal CYP17a1 mRNA expression, and the effect can be blocked by antibodies to inhibin-α or β-glycan (Hoang et al, 2013). The increased expression of ovarian CYP11a1 protein in thecal and interstitial cells, and in mural granulosa cells of large antral follicles after FSH + LH administration also supports our conjecture that sensitivity to LH depends on follicular development.…”

Section: Discussionmentioning

confidence: 99%

Effect of azaline B on follicular development and functions in the hamster

Chakraborty¹,

Roy²

2015

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

The usefulness of azaline B, a GnRH antagonist, in suppressing gonadotropin secretion in the golden hamster was examined by examining follicular development, steroidogenesis and expression of steroidogenic enzymes. Serum levels of P and E declined significantly, while FSH or LH was undetectable in azaline B-treated hamsters. FSH significantly increased serum E levels, whereas LH upregulated serum P levels. The formation of antral follicles ceased in azaline-treated hamsters, but was reversed by FSH with or without LH supplement. FSH also activated the primordial follicle pool resulting in increased formation of primary and preantral follicles. Further, an increasing trend in the formation of preantral follicles in response to E or E + P, and the formation of antral follicles in response to E + P treatment was evident. The level of Cyp11a1 mRNA increased markedly in LH− or LH + FSH-treated hamsters, whereas FSH with or without LH upregulated Cyp17a1, Cyp19a1 and Fshr mRNA expression. E without or with P also upregulated ovarian Cyp19a1 mRNA expression. The expression of enzyme protein corroborated the mRNA data. In summary, azaline B is an efficient GnRH antagonist in the hamster, and will be useful in studying the selective effect of gonadotropins on ovarian functions without disrupting the physiological functions of other hormones in ovarian cells.

show abstract

Paracrine regulation of theca androgen production by granulosa cells in the ovary

Cited by 21 publications

References 43 publications

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

Effect of azaline B on follicular development and functions in the hamster

Contact Info

Product

Resources

About