Medial Preoptic Area, Estrogen, and the Peripubertal Desensitization to the Negative Estrogen Feedback in Female Rats

Abstract

Bilateral lesions placed in the medial preoptic area (MPOA) markedly diminished the luteinizing hormone-(LH-) and follicle-stimulating hormone- (FSH-) inhibiting effects of s.c. injected or intrahypothalamically implanted estradiol benzoate (EB) in ovariectomized immature rats. Desensitization to the negative estrogen feedback was also recorded in immature rats implanted into the MPOA with a mixture of 1 part EB and 240 or 360 parts cholesterol. Estrogen implants located in the hypothalamic ventromedial-arcuate region were ineffective in this regard. Whereas precocious puberty resulted from the implantation of EB into the MPOA, a delay of puberty onset was induced by medial preoptic implants of the antiestrogen clomiphene citrate which also enhanced the LH-suppressing effect of s.c. administered EB in prepubertal females. It is proposed that an increase of the estrogen concentration in the MPOA inactivates medial preoptic neurons that exert a restraining influence on tonic LH (and FSH) secretion by sensitizing the mediobasal hypothalamus to the negative feedback action of estrogen. This mechanism may be involved in the control of the onset of puberty in female rats.

Influence of the Medial Preoptic Dopaminergic Activity on the Efficiency of the Negative Estrogen Feedback in Prepubertal and Cyclic Female Rats

“…Former studies [10][11][12] had shown that the sensitivity to the gonadotrophin, particularly the LH-inhibiting effect of estrogen, declines substantially in immature and cyclic female rats prior to the onset of puberty and during the preovulatory phase of the ovarian cycle, respectively. The desensitization of the negative estrogen feedback is proba bly induced by increasing estrogen levels in the blood [11,13], and preliminary results [16] suggested that inhibition of the medial preoptic DA activity might be involved.…”

“…The desensitization of the negative estrogen feedback is proba bly induced by increasing estrogen levels in the blood [11,13], and preliminary results [16] suggested that inhibition of the medial preoptic DA activity might be involved. The relationship between this activity and the sensitivity of the negative estrogen feedback was investigated in the present study.…”

“…This mechanism may essentially be involved in the control of female puberty and of the ova rian cycle [10,II,13]. The present findings suggest a possi ble relationship between the desensitization to the gonado trophin-inhibiting effect of estrogen and the medial preop tic DA neurotransmission, because (1) high DA activity in the MPOA enhanced, whereas low activity diminished, the inhibition of LH secretion by EB; (2) alteration of this acti vity markedly affected the onset of puberty and ovarian cy clicity, and (3) preliminary evidence was obtained sugges ting an inhibitory effect on the DA transmission in the MPOA of an estrogen treatment that induced desensitiza tion of the negative estrogen feedback.…”

“…Similar implants located in the VMAR were ineffective in this regard. The results suggest that: (1) low DA activity in the M POA reduces and high activity enhances the sensitivity of the negative estrogen feedback in immature and adult female rats; (2) the medial preoptic DA activity seems to be involved in the control of female puberty and of the ovarian cycle, and (3) a relationship may exist between the estrogen-induced prepu bertal and preovulatory desensitization of the negative estrogen feedback and the DA neurotransmission in the MPOA.Recent studies in female rats demonstrated that the sen sitivity to the gonadotrophin-inhibiting effect of estrogen declines prepubertally and during the preovulatory phase of the ovarian cycle [10][11][12]. Further results suggested that estrogen itself induces the desensitization process by an in hibitory action on the medial preoptic area (MPOA), be cause both the local implantation of very low amounts of estradiol benzoate (EB) and bilateral lesioning of this region diminished considerably the inhibition of gonado trophin secretion by estrogen in immature and adult rats [ 11,13].…”

“…Further results suggested that estrogen itself induces the desensitization process by an in hibitory action on the medial preoptic area (MPOA), be cause both the local implantation of very low amounts of estradiol benzoate (EB) and bilateral lesioning of this region diminished considerably the inhibition of gonado trophin secretion by estrogen in immature and adult rats [ 11,13].…”