Maturation of the Inhibitory Feedback Action of Oestrogen on Follicle-Stimulating Hormone Secretion in the Immature Female Rat: A Role for Alpha-Foetoprotein

Abstract

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11 beta-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0.00015 microgram R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0.05 to 0.01 microgram/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.

Age-Related Changes of Genital Systems in the Female Crj:CD(SD)IGS Rats during Sexual Maturation.

“…This is attributable to the high concentration of α-fetoprotein, which binds up the estrogens available around this age [1,10]. It is generally accepted that E2 is inactive when bound to α-fetoprotein.…”

Prepubertal increases in gonadotropin-releasing hormone mRNA, gonadotropin-releasing hormone precursor, and subsequent maturation of precursor processing in male rats.

“…Infantile rats (preweaning) are much less sensitive to the negative feedback of sex steroids on LH release (37,38) than juvenile rats (39)(40)(41)(42). One of the reasons for this is that in infants there are high serum levels of a-fetoprotein, which binds sex steroids (43).…”

“…One of the reasons for this is that in infants there are high serum levels of a-fetoprotein, which binds sex steroids (43). As a-fetoprotein levels decrease in the juvenile animal, more steroid becomes available to extragonadal tissues and the effectiveness of the steroid as a negative feedback agent increases (38,42,43). The results of our study are consistent with the gonadostat hypothesis in that they support the thesis that the effectors of the chronometer (gonadal steroids) are dependent on the prepubertal development and maturation (biosynthesis and release capacities) ofthe initiator (hypothalamic GnRH) (for reviews see references 1-7).…”

Toxicologic/carcinogenic Effects of Endocrine Disrupting Chemicals on the Female Genital Organs of Rodents

“…On the other hand, α-fetoprotein, the estrogen-binding protein produced in the liver, is found in very high concentrations for several weeks after birth 12 . It is well known that the increase of FSH before puberty is caused by nullification of the negative feedback of estrogen because of the high concentrations of serum α-fetoprotein 13 . A striking sexual dimorphism in gross morphology of the medial preoptic area (sexually dimorphic nucleus of the preoptic area: SDN-POA) has been recognized in the rat brain 14 .…”