Anti-Müllerian Hormone (AMH) May Stall Ovarian Cortex Function Through Modulation of Hormone Receptors Other Than the AMH Receptor. (August 2018)

• Record Type: Journal Article
• Authors: Detti, Laura; Fletcher, Nicole M.; Saed, Ghassan M.; Peregrin-Alvarez, Irene; Uhlmann, Rebecca A.
• Is Part Of: Reproductive sciences. Volume 25:Number 8(2018:Aug.)
• Page Start: 1218
• Page End: 1223
• Publication Date: 2018-08
• Subjects: recombinant AMH -- receptors -- AMH-R2 -- IGF1 -- inhibin B -- FSH -- LH -- PCOS -- cell proliferation; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719117737850
• Languages: English
• ISSNs: 1933-7191

Abstract

Objective: To test whether recombinant anti-Müllerian hormone (AMH) can inhibit ovarian cortex function by modulating the expression of other hormone receptors. Materials and Methods: Pilot experimental study with ovarian cortex obtained from 5 patients. Immediately after explant, the ovarian cortex specimens were divided into 5 equal fragments. One fragment was flash-frozen (uncultured) and 4 were incubated for 48 hours at 37°C in a pH-adjusted gamete buffer medium with increasing AMH concentrations of 0, 5, 25, and 50 ng/mL. After incubation, all specimens were rinsed and flash-frozen for polymerase chain reaction (PCR) executed in triplicates. We utilized real-time reverse transcription–polymerase chain reaction (RT-PCR) to determine messenger RNA (mRNA) levels of AMH and its receptor Anti-Müllerian Hormone-Receptor 2 (AMH-R2), follicle stimulating hormone receptor (FSH-R), luteinizing hormone receptor (LH-R), inhibin B, and insulin-like growth factor 1 receptor 1 (IGF1-R1) in ovarian cortex tissue. In addition, we performed Ki-67 immunostaining to evaluate cell proliferation in the treatment groups. Results: Absence of recombinant human AMH (rAMH) caused upregulation of all markers. Exposure to increasing rAMH concentrations caused tissue AMH expression downregulation ( P = .024), while AMH-R2 ( P = .005), FSH-R ( P = .009), LH-R ( P = .003), and inhibin B ( P = .001) mRNA expression followed a bell-shaped response with an increased expression at low dose, followed by a decreased expression at higher doses. Expression of IGF1-R1 was independent ( P = .039) of rAMH exposure. The Ki-67 immunostaining showed an increased cell proliferation in the media control compared to the uncultured and the tissue cultured with rAMH. Conclusions: Culture with increasing rAMH concentrations caused downregulation of its own, as well as other hormone receptors, and a decreased ovarian cortex cell proliferation. These results help understanding the inhibitory effects of AMH on follicular development.