Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line--derived neurotrophic factor in patients with Parkinson's disease. Report of two cases and technical considerations.

The authors have studied the ability of glial cell line-derived neurotrophic factor (GDNF) to promote survival of human fetal dopaminergic tissue after a storage period of 6 days and subsequent implantation into the human putamen. The results indicate that GDNF promotes survival of stored dopaminergic cells. Cells stored without GDNF had a 30.1% decrease in survival time compared with those exposed to GDNF. Two patients with Parkinson's disease received bilateral putaminal implants of fetal dopaminergic cells exposed to GDNF for 6 days and showed enhancement of graft survival as assessed by positron emission tomography scanning. A mean increase of 107% in putaminal fluorodopa uptake from baseline values was observed 12 months postgrafting.

Stimulation of estradiol production from estrone-3-sulfate by 5 alpha-dihydrotestosterone in cultured human placental explants.

The effect of androgens on the conversion of estradiol (E2) and estrone (E1) from estrone-3-sulfate (E1-S) was studied in explants of normal human term placentas. Explants incubated in medium supplemented with 2.0 microM E1-S showed that 50 microM dihydrotestosterone (DHT) stimulated E2 production 15-fold above control values after 0.5h, but neither 50 microM methyltestosterone (MT) nor 50 microM diethylstilbestrol (DES) had any effect. HCG (5.0 i.u./ml), alone or in combination with one of the androgens, did not influence the E2 production. When the explants were incubated in medium with 0.25 microM E1-S (the average concentration reported for late pregnancy plasma), DHT (0.5-50 microM) caused a dose- and time-dependent increase in E2 production, while E1 production and the combined accumulation of E2 and E1 were slightly inhibited by all doses of DHT during the 0.5-4h incubation. When E1 (0.1 microM) was used as substrate, DHT caused a dramatic dose- and time-dependent shift in the E1-E2 equilibrium towards E2. The results indicate that during late pregnancy, a particular class of androgens may increase the production of the more bioactive E2 from the circulating E1-S; the mode of action may be an enhanced conversion of E1 to E2.

Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception. III. Effect of preovulatory administration following the luteinizing hormone surge on ovarian steroidogenesis.

A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinylestradiol was administered orally at 18 hours after the detection of luteinizing hormone rise and again at 30 hours in five healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17 alpha-hydroxyprogesterone, and estradiol (E2) measured in a control (placebo) cycle with those in two consecutive treatment cycles. Treatment did not alter the steroid levels in one subject. P was suppressed in one or both treatment cycles of four subjects. E2 was suppressed in both treatment cycles of one subject and produced widely fluctuating patterns in another. The hormonal patterns in the two consecutive treatment cycles of the same individual were similar in all but one instance, where only the P level in the second treatment cycle was diminished. These results showed that this treatment can elicit steroidogenic responses of varying degrees and duration. The contraceptive action may lie in the altered P and/or E2 level at certain points in the menstrual cycle.

PIP: A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinyl estradiol was administered orally at 18 hours after detection of luteinizing hormone and again at 30 hours in 5 healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17alpha-hydroxyprogesterone, and estradiol (E2) measured in a control (placebo) cycle with those in 2 consecutive treatment cycles. Treatment did not alter the steroid levels in 1 subject. P was suppressed in 1 or both treatment cycles of 4 subjects. E2 was suppressed in both treatment cycles of 1 subject and produced widely fluctuating patterns in another. The hormonal patterns in the 2 consecutive treatment cycles of the same individual were similar in all but 1 instance, where only the P level in the 2nd treatment cycle was diminished. These results showed that this treatment can elicit steroidogenic responses of varying degrees and duration. The contraceptive action may lie in the altered P and/or E2 level at certain points in the menstrual cycle.

Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception. II. Effect of postovulatory administration on ovarian function and endometrium.

A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinylestradiol (EE) was administered orally at 36 hours after the detection of the luteinizing hormone peak and again at 48 hours in 12 healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17 alpha-hydroxyprogesterone, and estradiol (E2) in control (placebo) and treatment cycles. Five subjects showed no significant change in the levels of these steroids but had a shortened luteal phase. The treatment significantly decreased both P and E2 levels in three subjects, while two subjects showed diminished E2 levels only. The remaining two subjects had lower P levels and fluctuating E2 patterns. Endometrial biopsies from both study cycles indicated asynchronous development of the epithelial and stromal components in the treatment cycle. These findings (abnormal luteal phase steroid levels and duration and outphased endometrial development) indicate that corpus luteum function was variously affected by the action of norgestrel-EE treatment.

PIP: A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinyl estradiol (EE) was administered orally at 36 hours after detection of the luteinizing hormone peak and again at 48 hours in 12 healthy volunteers with normal menstrual cycles. The effects on ovarian functions were studied by comparing the daily serum levels of progesterone (P), 17alpha-hydroxyprogesterone, and estradiol (E2) in control (placebo) and treatment cycles. 5 subjects showed no significant changes in the levels of these steroids but had a shortened luteal phase. The treatment significantly decreased both P and E2 levels in 3 subjects, while 2 subjects showed diminished E2 levels only. The remaining 2 subjects had lower P levels and fluctuating E2 patterns. Endometrial biopsies from both study cycles indicated asynchronous development of the epithelial and stromal components in the treatment cycle. These findings (abnormal luteal phase steroid levels and duration and outphased endometrial development) indicate that corpus luteum function was variously affected by the action of norgestrel-EE treatment.