Experimental polycystic ovarian syndrome is associated with reduced expression and function of P2Y2 receptors in rat theca cells

• Published in: Molecular reproduction and development 2019-03, Vol.86 (3), p.308-318
• Main Authors: Campos‐Contreras, Anaí del Rocío, Juárez‐Mercado, Ana Patricia, González‐Gallardo, Adriana, Chávez‐Genaro, Rebeca, Garay, Edith, De Ita‐Pérez, Dalia Luz, Díaz‐Muñoz, Mauricio, Vázquez‐Cuevas, Francisco Gabriel
• Format: Article
• Language: English
• Subjects: Animals; Cell growth; Cell proliferation; Cell Proliferation - physiology; Cells, Cultured; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Kinases; Ovaries; P2Y receptors; P2Y2; Phosphorylation; polycystic ovarian syndrome (PCOS); Polycystic ovary syndrome; Polycystic Ovary Syndrome - pathology; Polymerase chain reaction; Promoter Regions, Genetic - genetics; Purine P2Y receptors; purinergic signaling; Purines; Rats; Rats, Wistar; Receptor mechanisms; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2Y2 - metabolism; Regulatory sequences; Signal Transduction - physiology; Testosterone; Testosterone - pharmacology; Theca; Theca Cells - pathology; Theca Cells - physiology; Transcription; Uridine Triphosphate - pharmacology
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.23106

Extracellular purines through specific receptors have been recognized as new regulators of ovarian function. It is known that P2Y2 receptor activity induces theca cell proliferation, we hypothesized that purinergic signaling controls the changes related to hyperthecosis in polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the expression of UTP‐sensitive P2Y receptors and their role in theca cells (TC) proliferation in experimentally‐induced PCOS (EI‐PCOS). In primary cultures of TC from intact rats, all the transcripts of P2Y receptors were detected by polymerase chain reaction; in these cells, UTP (10 μM) induced extracellular signal‐regulated kinases (ERK) phosphorylation. Rats with EI‐PCOS showed a reduced expression of P2Y2R in TC whereas P2Y4R did not change. By analyzing ERK phosphorylation, it was determined that P2Y2R is the most relevant receptor in TC. UTP promoted cell proliferation in TC from control but not from EI‐PCOS rats. The in silico analysis of P2yr2 promoter indicated the presence of androgen response elements; the stimulation of TC primary cultures with testosterone promoted a significant reduction in the expression of the P2yr2 transcript. We concluded that P2Y2R participates in controlling the proliferative rate of TCs from healthy ovaries, but this regulation is lost during EI‐PCOS. Extracellular purines through specific receptors have been recognized as new regulators of ovarian function. The aim of this study was to analyze the expression of UTP‐sensitive P2Y2 receptors and their role in theca cells from healthy and with polycystic ovarian syndrome (PCOS) rats. In cells from healthy rats, P2Y2 was functional and able to induce cell proliferation; but in cells from PCOS animals its expression was downregulated by the high levels of testosterone We concluded that P2Y2R participates in controlling the proliferative rate of theca cells from healthy ovaries, but this regulation is lost during PCOS.