Bernard Cantor

Distribution of cytoplasmic estrogen and progesterone receptors in human endometrium

Unoccupied estrogen receptors and progesterone receptors were measured in the cytoplasm of five sections along the length of endometrium obtained from noncancerous, premenopausal hysterectomy specimens. The concentrations of the two receptors were measured with tritiated estradiol or R5020 (a synthetic progestin), the latter two having been purified by high-pressure liquid chromatography, and were found to be highest in the fundus and lowest in the cervix. Progesterone receptor levels, ranging from 50 to 3,500 fmoles of R5020 bound per milligram of protein, were generally much higher in each section of the endometrium than estrogen receptor levels, which ranged from 0 to 500 fmoles of estradiol bound per milligram of protein. Near ovulation it seemed that the distribution profiles of both receptors became very steep, with more than a tenfold difference in the receptor levels being found between the fundus and the cervix. Receptor levels measured in endometrial samples obtained by curettage or aspiration should be interpreted with caution.

The uneven distribution of estrogen and progesterone receptors in human endometrium.

Abstract Estrogen (E 2 R) and progesterone (PgR) receptors were measured in the cytoplasm and/or nuclei from five sections along the length of benign human endometrium. For the cytoplasmic E 2 R and PgR determinations we used [ 3 H]-E 2 , [ 3 H]-R5O2O and dextran coated charcoal and analyzed the data by the Scatchard method. We observed a steep decrease of E 2 R and PgR levels (expressed as pmol [ 3 H]-steroid bound per mg soluble protein) from the fundal to the cervical sections; although endometrial E 2 R and PgR levels fluctuate during the menstrual cycle, this steep receptor gradient persisted throughout the cycle and after menopause. The equilibrium dissociation constants did not vary among the different sections, during the menstrual cycle or after menopause (mean ± SE: 0.22 ± 0.02 nM for E 2 R and 2.42 ± 0.18 nM for PgR). Nuclear E 2 R and PgR were measured by a “single-point” assay using [ 3 H]-E 2 and [ 3 H]-R5O2O, respectively. The average distribution patterns of nuclear E 2 R and PgR levels (expressed as pmol [ 3 H]-E 2 or [ 3 H]-R5O2O bound per mg DNA) were the reverse of those cytoplasmic E 2 R and PgR in all sections except the cervical, and were highest in the lower uterus. Future attempts to seek correlations between endometrial receptor levels and diagnoses of gynecologic disorders or clinical responses to therapy should take into consideration these uneven distribution patterns of cytoplasmic and nuclear E 2 R and PgR.

Carbohydrate Metabolism and the Semen Profile: Glucose, Insulin, and Sperm Studies

Twenty-seven men attending an infertility clinic received detailed studies of their ejaculate and carbohydrate metabolism. The latter was done using a 3-hour oral glucose tolerance test with a 100-gm glucose load and measuring both blood glucose and plasma insulin levels. There was no significant difference in either the blood glucose or the plasma insulin values between the men with normal sperm counts and those with abnormal sperm counts. These data suggest that mild subclinical states of carbohydrate abnormalities do not routinely alter male fertility.

Hormone Studies in a Gynandroblastoma

Plasma gonadotropin, testosterone, androstenedione, and estradiol levels were determined before and after removal of a 37-pound gynandroblastoma from an 18-year-old virilized, mentally retarded female. Testosterone and androstenedione levels preoperatively were in the normal female range and fell dramatically after castration. Histologic examination showed active atypical granulosa and Sertoli elements. The hormonal data obtained do not account for the marked virilization observed.

Cold pressor test in women: effect on vaginal blood flow.

Vaginal blood flow changes in women were evaluated qualitatively by heat-flow discs mounted on cooled vaginal probe. Statistically significant increases in vaginal blood flow, systolic blood pressure, and pulse rate were found in seven normal subjects during a 4 minute immersion of one hand in ice water.

The Effect of Gonadotropin-Releasing Hormone on Blood Glucose, Insulin, Luteinizing Hormone, and Follicle-Stimulating Hormone Levels

Sixteen women volunteers with menstrual irregularities were studied with an intravenous injection of 100 microgram of gonadotropin-releasing hormone (GNRH). Serial blood samples were obtained for 2 hours after the injection and assayed for their concentration of glucose, insulin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). There was a significant increase in the levels of both gonadotropins following the injection, with the peak for LH occurring at 30 minutes and the peak for FSH occurring at 90 minutes. There was a slight decrease in the glucose level at 45 minutes and in the insulin levels at 60 and 120 minutes. Because GNRH causes only minor changes in these parameters of carbohydrate metabolism, it would appear to be safe to use in women with ovulatory abnormalities secondary to diabetes mellitus.

Enhanced gamete interaction in the sperm penetration assay after coincubation with pentoxifylline and human follicular fluid**Presented at the 46th Annual Meeting of The American Fertility Society, Washington, DC, October 15 to 19, 1990.

OBJECTIVE To evaluate the effect of pentoxifylline and heat-inactivated human follicular fluid (FF) on performance in the sperm penetration assay (SPA) as a paradigm for the effect of these agents on human sperm-egg interaction in vivo and in vitro fertilization. DESIGN Semen specimens from men undergoing SPA testing for evaluation of suspected male factor infertility were coincubated with neat medium or media supplemented with pentoxifylline or human FF in a nonblinded manner. PARTICIPANTS Twenty male factor infertility patients. INTERVENTIONS Semen specimens were preincubated with: [1] pentoxifylline 0.25 mg/mL; [2] 10% human FF; [3] pentoxifylline+human FF; and [4] neat Biggers, Whitten, and Whittingham medium. MAIN OUTCOME MEASURES Differences in the rate of penetration of zona-free hamster oocytes. RESULTS Preincubation with either human FF or pentoxifylline produced a significant improvement in hamster egg penetration rates. Coincubation with a combination of human FF and pentoxifylline resulted in a significant enhancement of penetration as compared with single agent treatment. CONCLUSIONS Coincubation of sperm with human FF and pentoxifylline may provide a means of enhancing sperm activity for insemination and assisted reproduction.

The effect of acutely elevated blood glucose levels on luteinizing hormone and follicle-stimulating hormone release following an intravenous gonadotropin-releasing hormone injection.

The effects of an acute blood glucose increase on the capacity of the pituitary gland to release gonadotropins (luteinzing hormone [LH] and follicle-stimulating hormone [FSH]) were studied in 21 women. Each woman received two intravenous challenges of 100 microgram of gonadotropin-releasing hormone (GNRH). Between these injections the blood glucose level was increased in 10 of the women by orally adminstering 100 gm of glucose. Although there were significantly higher blood glucose and plasma insulin levels in the latter group, the LH and FSH response to the second GNRH injection was not different. There was also no significant relationship between the basal blood glucose level and the gonadotropin (LH and FSH) response to GNRH. Acute elevations of blood glucose do not appear to alter the ability of the anterior pituitary cells to release gonadotropins.

FACTORS INFLUENCING THE DYNAMICS OF GONADOTROPIN RESPONSE FOLLOWING BOLUS INFUSION OF LUTEINIZING HORMONE-RELEASING FACTOR IN WOMEN WITH MENSTRUAL ABNORMALITIES

Thirty-five women with menstrual abnormalities were given 100 microng of luteinizing hormone-releasing hormone (LHRH) by bolus intravenous injection in an attempt to simplify and quantitate the usefulness of this test in clinical management. Peak and total gonadotropin responses are highly correlated. Peak and total LH are significantly related to basal LH but no similar relationship could be established for follicle-stimulating hormone (FSH). There is no association between gonadotropin response and prolactin levels or body weight. Basal estradiol levels are inversely related to FSH response but not to LH response. It is concluded that the use of an intravenous 100-microng bolus of LHRH is of little use as a clinical test for the gynecologic endocrine patient.