Seiichi Matsumoto

Mode and site of action of clomiphene

Abstract Direct action of clomiphene citrate upon the hypothalamus, especially on the median eminence and the anterior hypothalamus was demonstrated by the increase of plasma and pituitary LH following the stereotaxic implantation of clomiphene into the rat brain. Subcutaneous 5 day injection of clomiphene also increased both LH release and synthesis in rats. FSH release from the pituitary increased transiently, but FSH synthesis was not simulated following both the subcutaneous injection and the intra-hypothalamic implantation of clomiphene. These results indicate the mode and site of action of clomiphene citrate in the induction of human ovulation.

Suppression of Ovulation with Human Chorionic Gonadotropin

A study of the ability of exogenous human chorionic gonadotropin (HCG) to inhibit ovulation is presented. 5 young women with regular menstrual cycles received injections of Primogonyl (HCG) in doses of 1000-5000 IU daily for 3-16 days. Ovulation was suppressed in 1 of 3 women taking the lowest does and in both women taking higher doses. The ovarian histology of the subjects showed marked luteinization of both granulosa and theca with various stages of atresia in most of the medium and large follicles. Successful suppression of ovulation appeared to be dose related and was dependent on the duration and timing of the injections. It is suggested that a hormonal mechanism may be involved in the induction of follicle atresia in the normal menstrual cycle.

A clinical and metabolic study of masculinizing arrhenoblastoma

A patient with virilizing arrhenoblastoma was investigated clinically and evidence of estrinization was noticed. Urinary excretions of FSH, estrogens, 17-KS, 17-OHCS, pregnanediol, and pregnanetriol were assayed. Dexamethasone suppression and ovarian stimulation were carried out and a differential diagnosis of the hirsute female was undertaken. Chromosomal studies were carried out on peripheral blood and revealed a normal female karyotype (46/XX). Incubation studies with dehydroepiandrosterone-4-C 14 and Δ 4 -androstenedione-4-C 14 as substrate revealed evidence of testosterone production. Almost all of Δ 4 -androstenedione was converted to testosterone, and the residue was very low. The presence and overproduction of testosterone are significant factors to be considered in order to explain the high degree of masculinization in the cases of arrhenoblastoma.

Estrogen synthesis by Brenner tumors

A case is reported of a 75-year-old woman with large bilateral Brenner tumors of the ovaries and with clinical and chemical evidence for estrogen secretion. After removal of these tumors, estrogenic findings disappeared On incubation, the tumor tissue converted androstenedione to estrone and estradiol. It is concluded that some Brenner tumors have an aromatizing enzyme system and thus can synthesize estrogens.

The induction of abortion and menstruation by the intravaginal administration of prostaglandin F2α

The efficacy of intravaginal administration of prostaglandin F2 alpha (PGF2alpha) in induction of abortion was determined in a clinical trial of 16 gravidas aged 21-38, parity 0-4, between the 6th-11th weeks of pregnancy. PGF2alpha tablet (50 mg) was inserted into the posterior fornix of the vagina and repeated at 1-2 hour intervals; dose range varied from 50-250 mg. Slight to severe labor-like pain was felt by all patients in the lower abdominal region 20 minutes-4 hours after PGF2alpha administration. Vaginal bleeding occurred within 30 minutes-8 hours. In all but 1 case, the fetus and the villi were expelled broken into small pieces. All 16 patients aborted, 7 completely and 9 incompletely. This form of administration is deemed efficacious as 3 patients aborted completely within 5 hours and 4 aborted completely between 15-18 hours. Bleeding in most cases occurred following the onset of abdominal pain, 30 minutes-8 hours after treatment. In another clinical trial, the efficacy of intravaginal administration of PGF2alpha in inducing menstruation was tested in 10 volunteers aged 31-40. Either 50 or 25 mg PGF2alpha tablets were used. The patients recorded their basal body temperature (BBT) every morning. Menstruation was successfully induced in 6 of 10 patients. 6 patients treated 2-3 days before the expected date of menstruation had menstrual-like bleeding 1-9 hours after PGF2alpha administration. 3 patients treated 5, 7, and 13 days (a day before BBT shift) before the expected date of menstruation did not have vaginal bleeding. 1 patient, with monophasic BBT who was treated 3 days before the expected menstruation, did not have menstrual bleeding. Amount of induced flow was more or less the same in most patients; duration of flow was normal in all cases. The mechanism of action of PG in menstruation induction is not known. The authors speculate that PGF2alpha mechanically stimulates separation of the superficial endometrium from the remainder of the uterine wall when the endometrium is in the premenstrual state. Side effects noted were nausea, diarrhea, pyrexia, slight flushing of the face, and headache.

Short- and Auto-Feedback Control of Pituitary FSH Secretion

In order to clarify a short- and auto-feedback control of FSH release from the anterior pituitary, changes in plasma and pituitary FSH and LH were investigated in rats with FSH implanted into the ME o