Frederick J. Auletta

Mechanism of luteolysis: Effect of estradiol and prostaglandin F2α on corpus luteum luteinizing hormone/human chorionic gonadotropin receptors and cyclic nucleotides in the rhesus monkey

Recent studies from our laboratory suggest that estrogen-induced luteolysis in the primate may be mediated through synthesis of prostaglandin F2 alpha (PGF2 alpha). To elucidate further the mechanism of luteolysis, normally cycling rhesus monkeys received intra-corpus luteum (CL) injections of estradiol (100 microgram), PGF2 alpha (500 microgram), or the appropriate vehicles on the seventh day after the preovulatory estradiol surge. Peripheral vein blood was drawn, at 30-minute intervals for 6 hours for progesterone and luteinizing hormone (LH) assays. Five hours after intra-CL injection, the CL was excised and the LH/human chorionic gonadotropin (hCG) receptor-binding activity and cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were measured. PGF2 alpha significantly (p < 0.05) lowered progesterone within 1 hour, while the time required for estradiol to lower progesterone significantly was 3.5 hours; there was no significant change in LH, Estradiol and PGF2 alpha significantly (p < 0.05) decreased the LH receptor-binding capacity at 5 hours, without any change in the binding affinity. Also PGF2 alpha significantly (p < 0.05) increased cGMP in the CL, while cAMP remained unchanged; estradiol treatment resulted in a significant (p < 0.05) increase in cAMP with no change in cGMP. This study suggests that estradiol and PGF alpha cause a decrease in progesterone secretion by a loss of the LH/hCG receptor and the PGF2 alpha may act further through the cGMP system.

Endocrine and clinical effects of estradiol and testosterone pellets used in long-term replacement therapy

Ten women with estrogen deficiency symptoms because of premature menopause [3], gonadal dysgenesis [3], or surgical menopause [4] received subcutaneous implants consisting of 25–75 mg estradiol (E2) with or without 75 mg testosterone (T). All had elevated plasma FSH, and LH, and low E2 prior to treatment. Plasma levels of FSH, LH, E2, T and estrone (E1) were measured by specific radioimmunoassay techniques prior to treatment, three times a week for the first week and once a week for up to 76 weeks after implantation.

The Effect of Intrauterine Progesterone Treatment on the Endometrial Prostaglandin F Content in the Rabbit

The effect on rabbit endometrial prostaglandin F caused by progesterone delivered directly to the uterus was investigated. Four groups of animals were used in the experiment: (1) no treatment (control); (2) an empty Silastic capsule (as an intrauterine device [IUD]) was inserted in one horn and the other horn was sham-operated; (3) a Silastic capsule releasing 150 microng of progesterone/day was placed in one horn and the other horn was sham-operated; (4) a Silastic capsule releasing progesterone was placed in one horn and the opposite horn received an empty Silastic capsule. In group 1, which received no treatment, no difference was noted. In group 2, the prostaglandin content of the horn containing an empty IUD was significantly higher than that of the sham-operated horn. In group 3, the same significant difference was noted between the prostaglandin content of the IUD-containing, progesterone-treated horn and the sham-operated horn. In group 4, no significant difference was observed between the horn containing an inert IUD and that containing a progesterone-releasing device. The addition of progesterone to an IUD does not significantly affect the elevated prostaglandin content of the endometrium caused by an inert IUD.

Lack of relationship between prolactin and adrenal steroidogenesis in the ovine fetus

The role of fetal prolactin (PRL) as a fetal adrenotropic hormone was investigated in eight chronically catheterized fetal lambs. Catheters were placed for measurement of plasma prolactin (PRL), cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A). Daily (9 AM) samples were obtained until the onset of labor. In four animals 2-Br-alpha-ergocryptine (BC) was administered subcutaneously (1 mg/12 hours) for 11 to 21 days prior to delivery. Four animals served as controls. No difference between groups was noted in the duration of gestation. PRL increased in the control animals from 8.4 +/- 2.4 to 43.0 +/- 5.6 ng/ml (mean +/- SEM) at the time of delivery whereas in animals that received BC it decreased within 24 hour of administration and remained below 3 ng/ml throughout the study period. No differences were noted in the concentration of F, DHEA, DHEA-S, and A between groups. These results suggest that PRL does not play a role in adrenal steroidogenesis or in the initiation of parturition.

Effect of oral estriol on cervical secretions and on ovulatory response in infertile women.

Estriol in oral doses of 0.25, 0.5, and 1.0mg was administered for 10 days prior to ovulation to six infertile women. All patients kept basal body temperature records and all had frequent examinations of the cervical mucus, the latter recorded as the modified cervical score. Plasma levels of follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and estriol were determined serially using specific radioimmunoassay techniques in one control cycle and in the three subsequent cycles of treatment. Ten other patients with infertility due to cervical factors were also treated with 0.25mg of estriol. Improvement of the cervical score was consistent and statistically significant during treatment with 0.25mg of estriol, while higher doses of this estrogen had less consistent and statistically not significant effect. The day of the plasma estradiol peak and gonadotropin surge was not changed by 0.25mg of estriol. However, a delay of2 to 9 days in the plasma estradiol and gonadotropin rise was observed in three of six patients receiving 0.5 and 1.0mg of estriol. Three conceptions occurred during treatment. It is concluded that the administration of estriol in a dose of0.25mg/day during the follicular phase of the cycle may be beneficial to infertile patients with a cervical factor. An improved cervical score results from a synergistic effect between endogenous estrogens and exogenous estriol. However, higher doses of estriol may postpone the endogenous estradiol surge and ovulation until after completion of treatment. Thus, no additive effect of endogenous estradiol and exogenous estriol on the cervical mucus is observed.

Antifertility effect of azastene mediated by prostaglandin

Azastene, a synthetic steroid of the androstano (2,3-d) isoxazole family, has been shown to terminate pregnancy in the rat and in the primate. Its antifertility effect in the rat is associated with a decrease of progesterone and an increase in prostaglandin F (PGF). Its mechanism of action has been explained by the ability of azastene to inhibit 3 β -hydroxysteroid dehydrogenase, thereby critically decreasing progesterone production. However, azastene-induced PGF release could be directly responsible for the decreased progesterone production and hence for its antifertility effect. To test this hypothesis PGF release associated witch azastene administration was blocked by indomethacin. In indomethacin-treated rats, azastene administered at day 10 of pregnancy failed to decrease uterine blood progesterone [100.6±11 (mean±SE) ng/ml (N=10) for azastene-indomethacin–treated rats versus 30.6±4.4 (mean±SE) ng/ml (N=10) for azastene alone; p