Effects of the natural endocrine disruptor equol on the pituitary function in adult male rats

Toxicology. 2013 Feb 8;304:69-75. doi: 10.1016/j.tox.2012.11.017. Epub 2012 Dec 7.


Equol (EQ), a potent biologically active metabolite of the soy isoflavone daidzein, interacts with estrogen receptors (ERs), however, as suggested recently, EQ may also exert anti-androgenic actions in androgen regulated tissues like prostate and seminal vesicles in adult male rats. However, data regarding a putative anti-androgenic activity of EQ on pituitary function in male individuals are still lacking. Therefore, we investigated the effects of EQ on androgen- and estrogen-regulated gene expressions in the pituitary and circulating luteinizing hormone (LH) and prolactin (PRL) levels in adult male rats. 3-Month-old male Sprague-Dawley rats (n=12 per group) were treated by gavage for 5 days with either EQ (100 and 250 mg/kg BW/day) or vehicle olive oil (1 ml/rat/day). As reference compound, the pure anti-androgenic drug flutamide (FLUT) was employed at a dose of 100 mg/kg BW/day. At day 5, animals were sacrificed. Levels of pituitary hormones and gene expression were measured by radioimmunoassays and quantitative TaqMan(®) real-time reverse transcription polymerase chain reaction, respectively. The present findings revealed that the pituitary mechanisms involved in the effects of EQ and FLUT were different due to the opposite changes in the mRNA expression levels of estrogen receptor subtype alpha (ERα)-, truncated estrogen receptor product-1 (TERP-1)- and -2 (TERP-2)-, gonadotropin releasing hormone receptor (GnRH receptor)-, beta-subunit of LH (LHβ)-, and gonadotropin alpha subunit (α-subunit) genes. EQ displayed typical ER-agonistic actions as shown by the significant increases in ERα-, TERP-1/-2 mRNA expressions and serum PRL levels along with the significant reduction in serum LH levels, whereas FLUT exerted opposite effects on gonadotropin secretion and expression. Taken together, our findings are the first in vivo data that upon sub-acute oral exposure of EQ show an estrogenic effect on reproductive endocrine activity of the pituitary in adult male rats. However, EQ did not exert anti-androgenic effects on male rat pituitary function as observed at the levels of mRNA expression of androgen- and estrogen-regulated genes and circulating pituitary hormones.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Equol / administration & dosage
  • Equol / toxicity*
  • Flutamide / pharmacology
  • Gene Expression Regulation / drug effects*
  • Luteinizing Hormone / metabolism
  • Male
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Pituitary Hormones / metabolism*
  • Prolactin / metabolism
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / genetics
  • Receptors, Estrogen / genetics
  • Reproduction / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction


  • Endocrine Disruptors
  • Pituitary Hormones
  • RNA, Messenger
  • Receptors, Androgen
  • Receptors, Estrogen
  • Equol
  • Flutamide
  • Prolactin
  • Luteinizing Hormone