Effects of 8-prenylnaringenin on the hypothalamo-pituitary-uterine axis in rats after 3-month treatment

Phytoestrogens are increasingly consumed in artificially high doses as herbal preparations and nutritional supplements. The flavanone 8-prenylnaringenin (8PN) is a potent phytoestrogen, but its benefits and risks after long-term application are poorly identified. Therefore, we tested two doses of 8PN and 17 beta-estradiol-3-benzoate (E2B) (effective doses: 6(.)8 and 68(.)4 mg/kg body weight (BW) of 8PN, and 0(.)17 and 0(.)7 mg/kg BW of 17 beta-estradiol (E2)) and compared their effects on uterine weight, pituitary hormones (LH, FSH and prolactin) and the expression of estrogen-regulated genes and of estrogn receptor (ER)alpha and ER beta in the hypothalalumus, pituitary and uterus. Both doses of E2 and the high dose of 8PN suppressed serum LH and FSH, and stimulated serum prolactin levels, uterine weight, and progesterone receptor, insulin-like growth Factor I and complement protein C3 mRNA transcripts. In the preoptic and the mediobasal areas of the hypothalamus, all treatments had negligible effects on ER alpha and ER beta and gonadotropin-releasing hormone (GnRH) receptor gene expression, while ER beta and GnRH receptor transcripts in the anterior pituitary were reduced under both E2 doses and the high 8PN dose. The mRNA concentrations of the LH alpha and -beta subunits in the pituitary were Suppressed by E2 and 8PN. In summary, 8PN had very similar though milder effects than E2 on all tested parameters. Inhibition of climacteric complaints by E2 takes place in the hypothalamus, where it inhibits the overactive GnRH pulse generator. Hence, 8PN may be used to inhibit climacteric symptoms effectively. Human pharmacologic studies will show whether the stimulatory effect on the uterus that was found in the present animal model would require the concomitant administration of progestins to prevent endometrial overstimulation.