In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers.hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time RT-PCR. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS).In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α (ERα), whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of pro-androgenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfo-transferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone (T) and dihydrotestosterone (DHT) secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genito-urinary syndrome in menopause.

Insight on the intracrinology of menopause: androgen production within the human vagina / Ilaria Cellai, Vincenza Di Stasi, Paolo Comeglio, Elisa Maseroli, Tommaso Todisco, Chiara Corno, Sandra Filippi, Sarah Cipriani, Flavia Sorbi, Massimiliano Fambrini, Felice Petraglia, Irene Scavello, Giulia Rastrelli, Gabriele Acciai, Fabio Villanelli, Giovanna Danza, Erica Sarchielli, Giulia Guarnieri, Annamaria Morelli, Mario Maggi, Linda Vignozzi. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - STAMPA. - 162:(2021), pp. 1-13. [10.1210/endocr/bqaa219]

Insight on the intracrinology of menopause: androgen production within the human vagina

Ilaria Cellai;Vincenza Di Stasi;Paolo Comeglio;Tommaso Todisco;Chiara Corno;Sandra Filippi;Sarah Cipriani;Flavia Sorbi;Massimiliano Fambrini;Felice Petraglia;Irene Scavello;Giulia Rastrelli;Fabio Villanelli;Giovanna Danza;Erica Sarchielli;Giulia Guarnieri;Annamaria Morelli;Mario Maggi;Linda Vignozzi
2021

Abstract

In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers.hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time RT-PCR. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS).In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α (ERα), whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of pro-androgenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfo-transferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone (T) and dihydrotestosterone (DHT) secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genito-urinary syndrome in menopause.
2021
162
1
13
Goal 3: Good health and well-being for people
Ilaria Cellai, Vincenza Di Stasi, Paolo Comeglio, Elisa Maseroli, Tommaso Todisco, Chiara Corno, Sandra Filippi, Sarah Cipriani, Flavia Sorbi, Massimi...espandi
File in questo prodotto:
File Dimensione Formato  
Cellai et al., 2021.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 679.75 kB
Formato Adobe PDF
679.75 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1217487
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 18
social impact