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392. Effect of 17β-estradiol on pituitary response to LHRH in ovariectomized rats and anovulatory women
Abstracts A. V., Department of Medicine, Tulane University School of Medicine, and VA Hospital, New Orleans, La. U.S.A. In order to investigate the possible interaction of endogenous steroids with exogenous estrogen on the pituitary response to LH-RH, we examined the effect of the administration of estradiol benzoate (EB} on the LB release induced by LW-RH in rats. Adult female rats were injected with 10 pg EB or sesame oil at 09.00 of every stage of the estrous cycle. Twenty-four hours later, 0.4pg of LH-RH was injected iv. under ether anesthesia and serum LH levels 20min after LH-RH were determined by radioimmunoassay. Some rats were treated with 5 kg EB at 09.00 on the day bf estrus, and the pituitary response to LH-RH was investigated at 13.00. 18.00 and 23.00 on the same day. The greatest response. was observed on the day of proestr& and estrus, and the lowest response on diestrous day 2. Pretreatment with EB always increased the pituitary response to LH-RH 24 h later, regardless of what stage EB was administered. In the control es&us rats which were injected with oil at 09.00, the greatest response to LH-RH was observed at 13.00 and the lowest at 23.00. In the estrus rats pretreated with EB at 9.00, the pituitary response to LH-RH was suppressed at 13.00 and 18.00, but did not change at 23.00 as compared with the response in the control estrous rats. The results provide further evidence that complex interactions of estrogen with other endogenous hormones affect the pituitary responsiveness to LH-RH. 392. Effect of 17jAstradiol oo pituitary response to LHRH in ovariectomized rats and anovulatory women SIMPSON,A. A., KULKARNI, P. N. and MACLEOD,S. C., Department of Physiology and Biophysics and Obstetrics and G~aecology, Dalhousie University, Halifax, Nova Scotia, Canada The aim of the studies is to determine the effect of 17/% estradiol on the pituitary response to LHRH. 17fi-estradiol (E,) was given to ovariectomized rats in doses of 0.0,0.4, 4~040~0and 400.0 pg/rat 24 h prior to treatment with SO0ng synthetic LHRH i.v. under urethane anesthesia. LH was measured in the serum at the time of LHRH administration and 20 min later. There was no change in the baseline LH concentration as a result of the E, treatment however; the changes in the LH concentration from baseline to 20min were 350 ng/ml and 114Ong/ml at 0.0 and 4OOgg E, respectively. A positive linear regression between the log of the pretreatment dose of E, and the change in serum LH ~on~ntration was indicated. There was no si~ifi~nt correlation between serum E, con~ntration in 15 women with anovulatory infertility and the baseline, peak or percent change in either LH or FSH levels following 100 fig LHRH s,c. Ethinyl estradiol treatment of anovulatory women, 50&day for 7 days results in a significant change in LH release in response to 1OOpg LHRH i.v. It is concluded that estradiol alters the sensitivity of the pituitary to LHRH.
11B. Steroid feedback on the hypothalamicpituitary axis
389
A recent challenge to the classical theory that a decrease in sensitivity to the suppressive effect of steroid occurs during puberty caused us to re-evaluate the concept in rats. Groups of rats were ovariectomized at 26,45 and 95 days of age and given estradiol replacement for the next 5 days. Serum FSH and LH were suppressed by much lower doses of estradiol (O.l5~g~kg/day) in the immature animals than in either of the mature groups (0.8-1.6pg/kg/day). Progesterone alone could not suppress either FSH or LH at doses up to 8 mg/kg/day in ovariectomized 26 or 95 day old female rats. Both mature and immature rats were given a constant low dose of estradiol that was sufficient to lower significantly, but not totally suppress, serum gonadotropins. Progesterone had a dose dependent effect in these animals. Low dose progesterone treatment causes gonadotropin suppression, particularly LH, in these animals, whereas higher doses of progesterone causes a significant stimulation and still higher doses brought about suppression. Therefore the effect of progesterone on gonadotropin secretion at various phases of the ovulatory cycle may be dependent on the ratio of estradiol to progesterone. (Supported by NIH research grant HD 04626-13). 394. Effect of gonadal steroids on the hypothalamic content of LH-RH in the rat FERLAND,LOUISE, COTE, J. and LABRIE, F., MRC Group in Molecular Endocrinology, Centre Hospitalier de l’universi te Laval, Quebec, Canada G 1V 4G2 Castrated adult male or female rats were injected twice daily for 7 days with increasing doses of estradiol benzoate, testosteronepropionateor progesterone before measurement of LH-RH hypothalamic content and pituitary and plasma LH levels. H~othalami~ LH-RH content was measured by bioassay using pituitary cells in monoiayer culture while LH levels were determined by RIA. Doses of estradiol higher than 0.01 pgLg/lOOg, B.W., led to an inhibition of plasma LH concentrations to approximately 20:/g of the control level in both male and female animals while the pituitary LH content remained unchanged. The LH-RH hypothalamic content was increased 2-fold in female animals treated with 0.01 ,ug estradiol benzoate while it remained unchanged at higher doses. In male animals, all doses of estradiol led to an important decrease of the hypothalamic LH-RH content (15 to 60% of the control level). The two doses of testosterone propionate used(25 and 125 pg/lOOg, B.W.) led to a decrease of the hypothalamic LH-RH content to approximately 30% of the control level in male animals while no effect was observed in female rats. Testosterone treatment did not affect pituitary LH content but the plasma LH levels were decreased to 5 to 15%of the control level in both male and female animals. The low dose of progesterone (O+pg/ IOOg, B.W.) led to an approximately 509;, decrease of hypothalamic LH-RH content whife the higher dose (2.0 mg) was accompanied by a 40”/ increase of the neurohormone level in male animals. Progesterone had no effect on pituitary or plasma LH levels in either male or female castrated rats and did not affect hypothalamic LH-RH content in female animals. 3%.
Feedback effect of gooadal steroids on the hypothalamic-pituitary axis LEYENDECKER,G., WILDT, L. and NOCKE. W., Abtlg fiir Gynlkologische Endokrinologie, Univ.-Frauenklinik, 53 Bonn, West Germany
393. Positive and negative feedback control of gwadotropin secretion by steroids in the maturiag rat ELDRIDGE,J. C., MCPHERSON,J. C., III and MAHESH, V. B., Department of Endoc~nology, Medical College The effect of gonadal steroids on the abrupt release of of Georgia, Augusta, Georgia 30902 U.S.A.
11B. Steroid feedback on the hypothalamicpituitary axis
389
A recent challenge to the classical theory that a decrease in sensitivity to the suppressive effect of steroid occurs during puberty caused us to re-evaluate the concept in rats. Groups of rats were ovariectomized at 26,45 and 95 days of age and given estradiol replacement for the next 5 days. Serum FSH and LH were suppressed by much lower doses of estradiol (O.l5~g~kg/day) in the immature animals than in either of the mature groups (0.8-1.6pg/kg/day). Progesterone alone could not suppress either FSH or LH at doses up to 8 mg/kg/day in ovariectomized 26 or 95 day old female rats. Both mature and immature rats were given a constant low dose of estradiol that was sufficient to lower significantly, but not totally suppress, serum gonadotropins. Progesterone had a dose dependent effect in these animals. Low dose progesterone treatment causes gonadotropin suppression, particularly LH, in these animals, whereas higher doses of progesterone causes a significant stimulation and still higher doses brought about suppression. Therefore the effect of progesterone on gonadotropin secretion at various phases of the ovulatory cycle may be dependent on the ratio of estradiol to progesterone. (Supported by NIH research grant HD 04626-13). 394. Effect of gonadal steroids on the hypothalamic content of LH-RH in the rat FERLAND,LOUISE, COTE, J. and LABRIE, F., MRC Group in Molecular Endocrinology, Centre Hospitalier de l’universi te Laval, Quebec, Canada G 1V 4G2 Castrated adult male or female rats were injected twice daily for 7 days with increasing doses of estradiol benzoate, testosteronepropionateor progesterone before measurement of LH-RH hypothalamic content and pituitary and plasma LH levels. H~othalami~ LH-RH content was measured by bioassay using pituitary cells in monoiayer culture while LH levels were determined by RIA. Doses of estradiol higher than 0.01 pgLg/lOOg, B.W., led to an inhibition of plasma LH concentrations to approximately 20:/g of the control level in both male and female animals while the pituitary LH content remained unchanged. The LH-RH hypothalamic content was increased 2-fold in female animals treated with 0.01 ,ug estradiol benzoate while it remained unchanged at higher doses. In male animals, all doses of estradiol led to an important decrease of the hypothalamic LH-RH content (15 to 60% of the control level). The two doses of testosterone propionate used(25 and 125 pg/lOOg, B.W.) led to a decrease of the hypothalamic LH-RH content to approximately 30% of the control level in male animals while no effect was observed in female rats. Testosterone treatment did not affect pituitary LH content but the plasma LH levels were decreased to 5 to 15%of the control level in both male and female animals. The low dose of progesterone (O+pg/ IOOg, B.W.) led to an approximately 509;, decrease of hypothalamic LH-RH content whife the higher dose (2.0 mg) was accompanied by a 40”/ increase of the neurohormone level in male animals. Progesterone had no effect on pituitary or plasma LH levels in either male or female castrated rats and did not affect hypothalamic LH-RH content in female animals. 3%.
Feedback effect of gooadal steroids on the hypothalamic-pituitary axis LEYENDECKER,G., WILDT, L. and NOCKE. W., Abtlg fiir Gynlkologische Endokrinologie, Univ.-Frauenklinik, 53 Bonn, West Germany
393. Positive and negative feedback control of gwadotropin secretion by steroids in the maturiag rat ELDRIDGE,J. C., MCPHERSON,J. C., III and MAHESH, V. B., Department of Endoc~nology, Medical College The effect of gonadal steroids on the abrupt release of of Georgia, Augusta, Georgia 30902 U.S.A.