Dynamics of gonadotropin and thienopyrimidine derivative TP03 effects on ovulation and ovarian steroidogenesis in Follimag-stimulated immature female rats

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Abstract

BACKGROUND: Gonadotropin preparations, particularly human chorionic gonadotropin (hCG), are commonly used to induce ovulation and treat reproductive disorders in women, albeit with associated side effects. Low-molecular-weight allosteric agonists of the luteinizing hormone receptor (LHR), such as thieno[2,3-d]pyrimidine derivatives, offer a potential alternative.

AIM: This study aims to compare the effects of thieno[2,3-d]pyrimidine TP03 and hCG on ovarian weight, corpus luteum formation, and plasma levels of estradiol, progesterone, and luteinizing hormone in immature female rats pre-treated with Follimag®. It also examines their impact on ovarian gene expression related to LHR and steroidogenesis.

MATERIALS AND METHODS: TP03 and hCG were administered 48 h after the Follimag® injection at a dose of 20 mg/kg (i.p.) and 15 IU/rat (s.c.), respectively. Parameters were assessed at 1, 2, 4, 8, 16, and 24 h after TP03 and hCG administration. Plasma hormone levels were measured via ELISA, and ovarian gene expression was analyzed using real-time PCR.

RESULTS: TP03 increased ovarian weight, progesterone levels in the blood, and expression of steroidogenic genes encoding the cholesterol-transporting protein StAR and the cytochromes CYP11A1 and CYP17A1. TP03 also stimulated corpus luteum formation (16–24 h after treatment). The temporal dynamics of its stimulating effects were similar to those of hCG, although their magnitude was slightly inferior to those of gonadotropin. TP03-induced decrease in blood estradiol levels and aromatase gene expression in the ovaries was also more moderate. Unlike hCG, which suppressed LHR gene expression 8 h after treatment, TP03 maintained a high LHR gene expression, preserving ovarian sensitivity to endogenous luteinizing hormone.

CONCLUSIONS: TP03 exhibits potential as an ovulation inducer with milder stimulating effects on ovarian steroidogenesis than hCG, which reduces the risks of developing ovarian hyperstimulation syndrome and resistance to gonadotropins.

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About the authors

Kira V. Derkach

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: derkatch_k@list.ru
ORCID iD: 0000-0001-6555-9540
SPIN-code: 6925-1558

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Andrey A. Bakhtyukov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: bahtyukov@gmail.com
ORCID iD: 0000-0002-2060-2020
SPIN-code: 7073-0586

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Viktor N. Sorokoumov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Saint Petersburg State University

Email: sorokoumov@gmail.com
ORCID iD: 0000-0002-4917-2175
SPIN-code: 1042-8142

Cand. Sci. (Chemistry)

Russian Federation, Saint Petersburg; Saint Petersburg

Egor A. Didenko

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Saint Petersburg State University

Email: didenkoegor58@mail.ru
ORCID iD: 0009-0000-5217-0624
SPIN-code: 5115-8389
Russian Federation, Saint Petersburg; Saint Petersburg

Irina V. Romanova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: irinaromanova@mail.ru
ORCID iD: 0000-0002-0348-0631
SPIN-code: 8891-8186

Dr. Sci. (Biology)

Russian Federation, Saint Petersburg

Irina Yu. Morina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: irinamorina@mail.ru
ORCID iD: 0000-0002-2252-0088
SPIN-code: 3489-8842

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Ivan A. Lebedev

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Author for correspondence.
Email: lebedevivan9@gmail.com
ORCID iD: 0000-0003-3917-4414
SPIN-code: 7084-4360
Russian Federation, Saint Petersburg

Lyubov V. Bayunova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: bayunoval@mail.ru
ORCID iD: 0000-0001-5543-8657
SPIN-code: 2833-2978

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Alexander O. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: alex_shpakov@list.ru
ORCID iD: 0000-0002-4293-3162
SPIN-code: 6335-8311

Dr. Sci. (Biology)

Russian Federation, Saint Petersburg

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