Adrenomedullin2 (ADM2)/intermedin (IMD) in rat ovary: changes in estrous cycle and pregnancy and its role in ovulation and steroidogenesis

Biol Reprod. 2015 Feb;92(2):39. doi: 10.1095/biolreprod.113.112854. Epub 2014 Nov 13.


Adrenomedullin2 (ADM2) is reported to facilitate embryo implantation and placental development. Therefore, the current study was undertaken to identify if ADM2 has a functional role in ovary to facilitate its reproductive actions. This study shows that the expression of ADM2 is differentially regulated in rat estrous cycle and that ADM2 increases the synthesis and secretion of 17beta-estradiol accompanied with an increase in the expression of steroidogenic factor 1 (Sf1), estrogen receptor Esr1, and enzymes involved in steroidogenesis in equine chorionic gonadotropin (eCG)-treated rat ovaries. In addition, inhibition of endogenous ADM2 function in eCG-treated immature rats caused impaired ovulation. Furthermore, the mRNA expression of Adm2 and receptor activity modifying protein 3 is higher in the ovary on Day 18 compared to nonpregnant and pregnant rats on Day 22. ADM2-like immunoreactivity is localized in granulosa cells, blood vessels, oocytes, cumulous oophorus, and corpus luteum of pregnant ovaries, suggesting a potential role for ADM2 in the ovary. This is supported by the presence of ADM2-like immunoreactivity in the corpus luteum during pregnancy and a decline in aromatase immunoreactivity in corpus luteum on Day 9 of gestation in rats infused with ADM2 antagonist during implantation and decidualization phase. Taken together, this study suggests a potential involvement of ADM2 in the rat ovary in regulating synthesis of estradiol to support ovulation and facilitate efficient implantation and placental development for a successful pregnancy.

Keywords: ADM2/IMD; ovary; ovulation; pregnancy; steroidogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenomedullin / genetics
  • Adrenomedullin / metabolism*
  • Animals
  • Corpus Luteum / drug effects
  • Corpus Luteum / metabolism
  • Estrous Cycle / drug effects
  • Estrous Cycle / metabolism*
  • Female
  • Gonadal Steroid Hormones / biosynthesis*
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Ovary / drug effects
  • Ovary / metabolism*
  • Ovulation / physiology*
  • Peptide Hormones / pharmacology
  • Pregnancy
  • Rats


  • Adm2 protein, rat
  • Gonadal Steroid Hormones
  • Neuropeptides
  • Peptide Hormones
  • intermedin (17-47)
  • Adrenomedullin