# The Stimulating Effect of Low-Molecular-Weight Luteinizing Hormone Receptor Agonist on Steroidogenesis and Ovulation in Female Rats with Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome

## TL;DR

This study shows that a new drug, TP03, can help induce ovulation and steroid hormone production in rats with PCOS, similar to a commonly used treatment.

## Contribution

The first evidence that allosteric LHR agonists like TP03 can effectively trigger ovulation in PCOS.

## Key findings

- TP03 increased progesterone levels and steroidogenesis gene expression in PCOS rats.
- TP03 induced corpus luteum formation and ovulation-related gene expression similar to hCG.
- Both PCOS cohorts responded to TP03 with improved ovarian function despite differing progesterone levels.

## Abstract

Polycystic ovary syndrome (PCOS) is associated with impaired ovarian steroidogenesis and ovulation, which necessitates the development of effective ovulation inducers for PCOS. The aim of the study was to evaluate the effects of allosteric luteinizing hormone receptor agonist TP03 and human chorionic gonadotropin (hCG) on ovarian steroidogenesis, as well as ovulation in prepubertal female rats with dehydroepiandrosterone(DHEA)-induced PCOS. Taking into account differences in progesterone levels, cohorts with high (PCOS(H)) and low (PCOS(L)) progesterone were formed and treated with Follimag and Cetrotide. After 48 h, TP03 (25 mg/kg) or hCG (25 IU/rat) were injected, and hormone levels, gene expression, and ovarian morphology were assessed. The PCOS(H)-cohort exhibited irregular estrous cycles, ovarian cysts, and increased ovarian mass and estradiol levels, but the number of corpora lutea (CL) was maintained. In the PCOS(L)-cohort, ovarian weight was increased, and Star, Cyp11a1, and Adamts1 gene expression as well as the CL number were decreased. In both cohorts, TP03 and hCG increased progesterone levels and the expression of steroidogenesis (Star, Cyp11a1) and ovulation (Cox2, Adamts1, Egr1) genes, as well as inducing CL formation. Thus, TP03, like hCG, stimulates steroidogenesis and ovulation in PCOS-rats with different progesterone levels, which provides the first evidence of the effectiveness of allosteric LHR agonists as ovulation triggers in PCOS.