Hypothalamic-pituitary function in neonatally oestrogen-treated male rats

Abstract

Neonatal oestrogen administration to male rats permanently impaired the function of the pituitary-testicular axis possibly by inhibiting neonatal gonadotrophin secretion. To analyse the hypothalamus and/or pituitary involvement in this inhibition, pituitary responsiveness to acute stimulation with LH-releasing hormone (LHRH) was studied in vivo and in vitro in Wistar male rats injected on day 1 of age with oestradiol benzoate (OB) or olive oil. FSH and LH pituitary content and plasma concentrations were reduced in oestrogenized male rats at days 10 and 16 of age. Likewise, the in-vivo increase in gonadotrophin plasma concentrations after acute stimulation with LHRH was almost completely suppressed in 10- and 16-day-old oestrogenized males. In vitro, the increased secretion of FSH after LHRH stimulation was abolished and the LH response strongly reduced in pituitaries from oestrogenized males. Finally, the effects of neonatal oestrogenization were not abolished by treatment from day 1 to day 15 with an LHRH agonist (0.01 microgram/kg per 12 h). We conclude that in male rats the effects of oestrogenization are due to both a reduction in LHRH endogenous secretion and a decrease in the pituitary responsiveness to LHRH.

Neonatal exposure to estrogen differentially alters estrogen receptor alpha and beta mRNA expression in rat testis during postnatal development

“…In keeping with previous references (Kincl et al 1965, Brown-Grant et al 1975, Bellido et al 1985, 1990, Pinilla et al 1992, neonatal administration of EB (500 µg/ rat; day 1) resulted in permanent atrophy of testes, and significantly decreased serum FSH, LH and testosterone levels during the study period. Finally, neonatal administration of LHRH-ANT (5 mg/kg every 72 h; days 1-15) induced a significant reduction in testicular weight on days 15 and 45 of age, as well as significant decreases in serum FSH, LH and testosterone values on day 15 of age.…”

“…In addition, prominent expression of AR has been identified in Sertoli cells during prepubertal development, a period when ARs are also abundant in peritubular myoid cells and interstitial cells (Bremner et al 1995). On this basis, the decrease in the relative levels and total expression of ER and AR mRNAs could be attributable, at least partially, to impaired development of testicular cell types expressing these genes after neonatal estrogenization , Pinilla et al 1992. However, the increase in the expression of ER mRNA in this experimental model cannot be explained through alterations in the cellular composition of the testis, as it is well established that neonatal exposure to estrogen impairs/delays maturation of germ, Sertoli and Leydig cells within the developing male gonad , Pinilla et al 1992.…”

“…To this end, 1-day-old male rats were injected s.c. with a single dose of EB (500 µg/rat); this protocol was selected on the basis of our previous studies as it was found to be the most effective in inducing complete estrogenization in the male rat (Aguilar et al 1984, Bellido et al 1985, 1990, Pinilla et al 1992. Vehicle (oil)-injected rats served as controls.…”

“…In male rodents, it is well established that exposure to supra-physiological doses of estrogens during the critical period of neonatal differentiation results in an array of permanent reproductive defects, which include atrophy of testes and sexual accessory glands (Kincl et al 1965, Brown-Grant et al 1975, Aguilar et al 1984, Newbold & McLachlan 1985, Naslund & Coffey 1986, impaired maturation of germ, Sertoli and Leydig cells (Gaytán & Aguilar 1986, Pinilla et al 1992, altered luteinizing hormone (LH) secretion (Aguilar et al 1984, Pinilla et al 1995, and inappropriate puberty onset (Brown-Grant et al 1975, Bellido et al 1985. Disruption of reproductive function by neonatal estrogenization is probably a multifaceted phenomenon, and complete elucidation of the mechanism(s) involved is still pending.…”

Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

“…Our results are in agreement with these studies and confirmed that all of the analyzed substances, including natural estrogen, had the detrimental effect on the germ and Sertoli cells number, as well as on the testis weight, diameter and length of seminiferous tubules. One of the possible explanation of this negative impact is that high levels of estrogen may cause a reduction in both GnRH secretion and pituitary responsiveness to GnRH [34], as well as the decrease in FSH and LH blood concentration, and as a consequence in testosterone production [35]. However, the direct effect of estrogen on testicular cells cannot be ruled out.…”