Comparative analysis of blood plasma epidermal growth factor concentrations, hormonal profiles and semen parameters of fertile and infertile males.

The relationship between male reproductive function and the blood plasma level of epidermal growth factor (EGF) is of interest in the light of the role that circulating EGF appears to play in regulating mouse spermatogenesis. We measured the concentrations of EGF in the blood plasma of 39 fertile men (sperm count > 20 x 10(6)/ml) and compared them with those of 31 infertile men (sperm < 20 x 10(6)/ml). Blood plasma levels of follicle stimulating hormone (FSH), luiteinising hormone (LH), prolactin and testosterone were also determined. The infertile patients had mean blood plasma EGF concentrations of 0.75 +/- 0.10 ug/L. The value was significantly lower than that of the fertile group (1.28 +/- 0.14 ug/L; P < 0.005). There were statistically significant differences between the fertile and infertile groups in sperm count, sperm viability, mean forward progression, testosterone, LH and FSH (P values between 0.0001 and 0.023). There was no significant difference in the prolactin concentrations between the two groups. Although overall average blood plasma EGF concentrations are significantly lower in the infertile males, regression analysis failed to reveal any direct relationships among the various parameters studied.

Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes.

The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

Purification and preliminary characterization of guinea pig testicular proteinase inhibitors.

Three guinea pig testicular, low-molecular-weight, acid-stable inhibitors specific for trypsin-like proteinases were isolated, purified, and characterized. The procedure comprised acid extraction of testicular acetone powder, pH precipitation of the extract, gel filtration of the supernatant on Sephadex G-100 and G-50, ion-exchange chromatography on SP-Sephadex, followed by QAE-Sephadex. Final purification was by rechromatography on Sephadex G-50 superfine gel. The three proteinase inhibitors were labeled A, B, and Cnb, the latter to denote nonbinding of Cnb to the QAE-Sephadex. Components A and Cnb showed competitive, whereas B showed noncompetitive, inhibition against trypsin. All three inhibitors were active against trypsin but were ineffective against chymotrypsin. The inhibition constants, Ki, were obtained using trypsin-catalyzed hydrolysis of the N-benzyloxycarbonyl-L-arginyl amide of 7-amino-4-trifluoro-methylcoumarin (CBZ-Arg-AFC) at pH 8.0. The values were calculated to be, for A, 1.5 x 10(-8) M; for B, 1.5 x 10(-8) M; and, for Cnb, 2.2 x 10(-7) M. The Ki values calculated from inhibition of trypsin-catalyzed hydrolysis of the active site titrant 4-methylumbelliferyl-p-guanidinobenzoate (MUGB) using Easson-Stedman plots were, for A, 7.7 x 10(-9) M; for B, 6.7 x 10(-9) M; and, for Cnb, 1.4 x 10(-7) M. The Mrs as determined by active site titration with MUGB were A, 11.2 kDa; B, 10.5 kDa; Cnb, 17.0 kDa. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave Mr values for A of 11 kDa, for B of 4 kDa, and for Cnb of 19 kDa. The discrepancy in Mr values for B indicates that it may function as a dimer or trimer in the active state.

A comparative study of three oral contraceptives in Ibadan: Norinyl 1/35, Lo-Ovral and Noriday 1/50.

A study of three combined oral contraceptives, Norinyl 1/35, Lo-Ovral and Noriday 1/50, was conducted at the University of Ibadan Teaching Hospital, Ibadan, Nigeria, to determine if there were differences in continuation rates and reasons for discontinuation. This report includes analysis of 150 women, all of whom were interval patients, randomly allocated to one of the above oral contraceptives between May 1984 and February 1985. Follow-up visits were scheduled at 1, 4 and 8 months after admission. Significantly more women in the Norinyl 1/35 group (P less than 0.05) reported intermenstrual bleeding, as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Lo-Ovral group. There were no other differences between the groups for side-effects. The continuation rates at 8 months were 90.8% for the Norinyl 1/35 group, 94.4% for the Lo-Ovral group and 87.1% for the Noriday 1/50 group. The corresponding rates for those lost to follow-up were 26.0, 40.8 and 17.7. The rate for total discontinuations (all discontinuations including women lost to follow-up) was 34.0% for the Norinyl 1/35 group, 44.9% for the Lo-Ovral group and 29.4% for the Noriday 1/50 group. There was a significant difference in lost to follow-up rates between the Lo-Ovral group and the Noriday 1/50 group (P less than 0.05). There were no other significant differences between the groups for life table rates (P greater than 0.05). There were no pregnancies reported during the study period.

Guinea pig testicular proacrosin-acrosin system: preliminary immunological characterization.

In this study, immunochemical techniques were employed to examine the guinea pig (GP) testicular proacrosin-acrosin system. Monospecific polyclonal antibodies to the highly stable enzymatically active 34,000 molecular weight form of GP testicular acrosin were generated. Western blot analysis of acid extracts prepared from snap-frozen freshly excised GP testes revealed two major immunoreactive bands with mol. wts of approximately 62,000 and 48,000 and one minor band with an approximate mol. wt of 54-56,000. The 62,000 mol. wt molecule identified is in close agreement with the previously reported mol. wt for purified GP testicular proacrosin. Western blot analysis of different species of testicular acid extracts demonstrated the evolutionary relatedness of the proacrosin-acrosin systems since immunoreactivity was observed primarily with acid extracts from rodent species (rat, mouse and hamster) and not with extracts from evolutionarily less-related species (goat, ram and bovine). The majority of the cross-reactivity observed was characterized by immunoreactivity with the 62,000 and 48,000 mol wt molecules. The only species which exhibited cross-reactivity with the 54-56,000 mol. wt protein was rat. In addition, the iso-immunogenic and aspermatogenic properties of the 34,000 mol. wt form of GP testicular acrosin were examined. One out of five Hartley and one out of seven Strain 2 female GPs immunized and boosted with a total of 200 micrograms of purified protein exhibited increased levels of circulating anti-acrosin iso-antibodies. The antigenic specificity of the iso-antibodies observed in the two animals was verified by Western blot analysis. All other female animals, including two strain 13 GPs, exhibited very low or undetectable levels of such antibodies following immunization. One out of three male Hartley GPs immunized with 50 micrograms of the purified protein exhibited typical lesions of experimental allergic orchitis while none of a group of three animals developed lesions at a 5 micrograms dose. Taken together, these results suggest that the 34,000 mol. wt form of GP testicular acrosin is neither a highly potent iso-immunogen nor aspermatogenic autoantigen.

Experience with the use of depo-medroxyprogesterone acetate in a Nigerian population.

Eight hundred and ten patients who accepted to use depo-medroxyprogesterone acetate (DMPA) for contraception were studied over a period of 11 years (1976-1986). Important side-effects observed were amenorrhoea (36.3%), weight gain (15.8%), weight loss (10.6%), metrorrhagia (6.7%) and menorrhagia (6.0%). Amenorrhoea, menorrhagia and metrorrhagia were major reasons for discontinuation of DMPA in 11% of acceptors. There were no cases of pregnancy, genital or breast malignancies during DMPA use. Our experience indicates that DMPA as a contraceptive is effective and should be available for suitable clients who demonstrate oestrogen intolerance.

PIP: A study was conducted in Ibadan, Nigeria over a period of 11 years, 1 January 1976 to 31 December 1986, on 810 patients who agreed to use depo-medro progesterone acetate (DMPA) for contraception. DMPA is a long-acting injectable contraceptive agent which provides protection over a period of time. It is given on a 3-monthly basis, and is thought to be an ideal contraceptive agent for women who have a poor compliance with taking oral contraceptives or do not wish to run the risk of using an intrauterine device. The women's medical histories were recorded and each of the women were thoroughly examined; women with hypertension, diabetes mellitus, positive cervical cytology, or irregular menstrual patterns were excluded from the study. The women were given 3-monthly intramuscular injections, and at each visit all side-effects reported were recorded. If the patient decided to discontinue use, the reasons were also noted and recorded. The results of the study are as follows. 490 (60.5%) of the women had protection for between 3 months and 12 months; 230 (28.4%) had protection for 13-24 months; while only 90 (11.1%) had protection for 25-33 months. Side effects noted were amenorrhoea (36.3%), weight gain (15.8%) and loss (10.6%) abnormal bleeding patterns (12.7%), and minor symptoms such as headaches (2.5%), dizziness (1.5%) and palpitations (1.1%). Reasons for discontinuation included amenorrhoea (16.2%), abnormal bleeding habits, (7%), hypertension (2.2%), and/or the desire to get pregnant (2%). Further discussion is given to the use of DMPA as an enhancement for lactation and an effective option to oral contraceptives.