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  • Title: Experimental studies on the positive feedback effect of progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone on the pituitary release of LH and FSH in the human female. The estrogen priming of the progesterone feedback on pituitary gonadotropins in the eugonadal woman.
    Author: Leyendecker G, Wildt L, Gips H, Nocke W, Plotz EJ.
    Journal: Arch Gynakol; 1976; 221(1):29-45. PubMed ID: 989265.
    Abstract:
    Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming. The hypothesis that progesterone (P) is involved in the regulation of the estradiol-induced midcycle surge of luteinizing hormone (LH) was investigated in eugonadal women. The administration of P during the midfollicular phase did not exert a positive feedback effect on serum levels of LH and follicle stimulating hormone (FSH). Serum estradiol levels fell after the administration of P, though levels of LH and FSH were not altered. This indicates a direct ovarian effect of P. Administration of P, in the presence of preovulatory levels of estradiol or exogenous ethinyl estradiol, induced an LH discharge indicative of the necessity of estradiol priming for the positive feedback effect of P. It was found that estradiol benzoate had to be adminstered at least 24 hours prior to the administration of P during the midfollicular phase for the LH surge to occur. In his latter experiment, neither P nor estradiol by themselves were able to produce an LH surge, thus indicating the estrogen priming is required for the positive feedback effect of P on LH release. 20alpha-dihydroprogesterone, but no 17-hydroxyprogesterone, was able to induce an LH surge with adequate estrogen priming.
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