Administration of a VIP-antagonist in vivo modifies ovarian hormone secretion in a rat model with polycystic ovary syndrome

Life Sci. 2021 Jan 15:265:118792. doi: 10.1016/j.lfs.2020.118792. Epub 2020 Nov 18.

Abstract

Aims: In the cyclic rat in estrus, the vasoactive intestinal peptide (VIP) has an impact on ovarian function, which depends on the endocrine status of the animal. In this work, we aimed to clarify the participation of VIP in the pathophysiological condition of polycystic ovary syndrome (PCOS) using a model of PCOS induced by estradiol valerate (EV-PCOS) in rats.

Main methods: In the cyclic rat in estrus and in the EV-PCOS model, we analyzed the acute effects of blocking VIP receptors with the use of an antagonist (Ant-VIP) injected into the left or right ovarian bursa on the steroidogenic response and ovarian catecholamine levels.

Key findings: In the cyclic animal in estrus, the treatment with Ant-VIP in the left ovarian bursa resulted in a reduction in testosterone serum levels and in ovarian levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), without changes in 4-hydroxy-3-methoxyphenyl (MHPG) and norepinephrine (NE). When the treatment was applied on the right side, only MHPG levels increased. In the EV-PCOS model, the treatment with Ant-VIP in the left ovarian bursa increased testosterone, estradiol, MHPG, and NE levels. When the treatment was performed on the right side, progesterone levels decreased and estradiol increased, without changes in ovarian catecholamines.

Significance: The binding of VIP to its receptors differentially regulates steroidogenesis in the cyclic animal in estrus and in the EV-PCOS model. The blocking of VIP signaling produces changes in ovarian catecholamines.

Keywords: Ovary; Polycystic ovary syndrome; VIP; VPAC receptors.

MeSH terms

  • Animals
  • Catecholamines / metabolism
  • Disease Models, Animal*
  • Estradiol / metabolism
  • Estradiol / toxicity
  • Female
  • Ovary / drug effects
  • Ovary / metabolism*
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / drug therapy
  • Polycystic Ovary Syndrome / metabolism*
  • Rats
  • Receptors, Vasoactive Intestinal Peptide / antagonists & inhibitors*
  • Receptors, Vasoactive Intestinal Peptide / metabolism*
  • Testosterone / metabolism
  • Vasoactive Intestinal Peptide / antagonists & inhibitors
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Catecholamines
  • Receptors, Vasoactive Intestinal Peptide
  • Vasoactive Intestinal Peptide
  • Testosterone
  • Estradiol