142. FSH and LH content of plasma after mitomycin treatment and the effect of the antibiotic on ovarian cellular constituents

842

Abstracts Institute for Research in Reproduction, Bombay-l 2. and Department of Biochemistry, Calcutta University. Calcutta-19. India

In the present study the effect of cannabis extract and its active component delta-9-tetrahydrocannabinol (A’-THC) on female reproduction has been studied. In the prepubertal rats the drug antagonised estradiol and triggered biochemical changes at the uterine level. Subsequent studies indicated that the drug inhibited steroidogenesis in the adult female ovary in addition to reducing the estradiol content. More important was the effect of delta-9-THC on the circulating serum and pituitary gonadotrophic hormones as well as on hypothalamic releasing hormone.

139. Elfect of ergocryptine on prolactin binding to mammary glands of mice treated with estradiol

SHETH. Cancer Bombay duction

N. A.. TIKEKAR. S. S. and SHETH. -A. R..* Research Institute. Tata Memorial Centre. 400012. and *Institute for Research in Repro(ICMR). Bombay 400012. India

One of the most intriguing problems pertaining to the hormonal control of murine mammary tumourigenesis is the intricate interrelationship of prolactin (PRL) and estradiol (EB) in this neoplastic process. Since binding of a hormone to specific receptors in a target tissue is the initial step in action of a hormone. we investigated the in riro effect of various doses of EB on [ “‘I]-rPRL binding to murine mammary glands. We observed that compared to ovariectomized controls. injections (s.c.) of EB at 5yg dose (for 8 days) significantly increased the [“‘I]-rPRL binding concurrent with an increase in serum PRL. In contrast. treatment with higher doses of EB (IO and 25 pg) decreased the binding as well as the serum PRL concentrations in comparison to those observed in 5ilg EB treated mice. To see whether the observed effect of EB on PRL binding was due to its direct action on the mammary gland or through enhanced PRL release. EB was administered simultaneously with CB-154. a potent inhibitor of PRL release. CB-I54 significantly decreased serum PRL concomitant with a decrease in binding even in the presence of EB. These results indicate that lower doses of EB act in synergism with PRL while high doses of EB interfere with the action of PRL on the target tissue.

140. Use of antibiotics study

of

receptor

and ‘la-methylated steroids in the binding and nuclear retention of

androgens

CHAN. K. M. B.* and LIAO. S..t *Department of Anatomy. University of Hong Kong. Hong Kong. and tThe Ben May Laboratory for Cancer Research and Department of Biochemistry. University of Chicago. Chicago. Illinois. U.S.A. The Sa-dihydrotestosterone (DHTtreceptor complex prepared from the cytosol fraction of rat ventral prostate can be retained tightly by isolated prostate cell nuclei. This process was not inhibited by high concentrations of rifamytins (AF/013 and AF/05). rifampicin. or actinomycin D. Similar results were obtained when the nuclear membranes were removed, before the experiment, by a medium containing Triton X-100. If the nuclear preparations were replaced by chromatin reconstructed from calf thymus DNA and prostate nuclear proteins. however, the receptor retention was markedly suppressed by actinomycin D. and by rifamycins that can inhibit mammalian RNA polymerase activity. Rifampicin that can inhibit the bacterial, but not the mammalian RNA polymerase activity did not inhibit retention. The receptor binding affinity and the androgenicity of l9-nortestosterone and related androgens can be

enhanced significantly by methylation of the 7z-positton on ring B of the steroid nucleus. Similarly. 7a. 17. \7-trimethylgona-4, l3-dien-3-one (TMGD) and ‘Ix-methyl- l9norandrost-4-ene-3. I7-dione bind more tightly to the prostate receptor protein than adrost-4-ene-3. l7-dione. even though they lack the l7/?-hydroxy group. TMGD can compete well, in cell-free systems. with DHT for receptor binding and nuclear retention. but these effects were not observed in riw or during the incubation of minced prostate. If this was due to the inability of TMGD to enter the prostate cells. the 7x-methylated I I-deoxysteroid and related compounds may be useful in the study of cell membrane transport of steroids.

141. Cyproheptadine-a potent prostaglandin antagonist GUPTA. 0. P. and ATAL. C. K., Department of Pharmacology. Regional Research Laboratory. JammuTawi. India In the course of an investigation it was observed that the uterine stimulant effect of prostaglandin FZ (PGF2) was blocked after the pretreatment of the tissue with cyproheptadine. This encouraged us to study in detail the prostaglandin antagonist activity of cyproheptadine in a number of irl rim and if1 ciao preparations. Cyproheptadine was found to antagonize the action of PGF2 in extremely low doses as follows:--Rat fundus. 3 x IO- I6 g;ml: Guinea-pig ileum, 6 x lo-l6 g,ml: Rabbit jejunum. 9 x 10-‘hg;ml: Rabbit uterus. 3 x IO- ” g/ml. In the cumulative dose-response curves of PGF*. cyproheptadine caused a parallel shift to the right without depressing the maximal responses at low doses whilst at higher doses these responses were depressed (I x IO-” g,ml - 6 x IO-” giml). The responses of other agonists on these preparations were blocked at much higher concentrations. Pressor or depressor responses of PGF, on the blood pressure of rabbit. dog and chicken were markedly inhibited with 30-ICO~cg;kg doses of cyproheptadine. Methysergide. another known 5-HT antagonist showed no prostaglandin antagonist activity. Keeping in view the role of prostaglandins in different pathophysiological conditions. cyproheptadine as a potent prostaglandin antagonist would be expected to prove effective as an antipyretic. anti-inflammatory and anti-diarrhoeal agent and in rheumatoid arthritis. asthma. dysmenorrhoea. premature labour or threatened abortion.

142. FSH and LH content of plasma after mitomycin treatment and the effect of the antibiotic on ovarian cellular constituents

DEB. C.. MAJUMDAR.G.. GHOSH. K.. MUKHERJEE.R. and BAGCHI. P.. Department of Physiology. Calcutta University. Calcutta700009 Mitomycin C. an antitumor drug has been found to suppress the activities of the enzymes succinic dehydrogenase. glucose-6-phosphate dehydrogenase and A5-3b hydroxysteroid dehydrogenase in the ovaries of sexually mature rats local&d histochemically. The same treatment also produces an increase in cholesterol content from control level (I.1 + 0.07 mg per 100mg)acfi~ th;oeate~on;r~ and ascorbic (1.99 + 0.19) (48.20 + 2.25 pg per 100 mg) to treated (68.45 & 4.74). The DNA content of ovaries decreased from control level of (762 + 42.01 mg per IOOmg) to the treated one (566 f 39.61). Radioimmunoassay of gonadotrophic hormones of serum revealed a significant increase in FSH from control level of 2.15 f 0.5pm per ml of serum to drug treated (3.76 +_ 0.14). LH level was also elevated from control 1.36 + 0.12 pm to treated (3.51 + 0.18). The rest@ indicate that the steroidogenic capacity of ovaries 1s

843

Abstracts reduced following

Mitomycin

C treatment

possibly due IO

its direct effect on ovarian DNA content. The low level of circulating ovarian hormone stimulated the pituitary to increased synthesis of gonadotrophins.

143. /r aitro effect of steroid hormone on tbe blastogenesis of peripheral blood lymphocytes HECDE, U. C., TEZABWALA, B. and RAO- S. S., Institute for Research in Reproduction. Parel. Bombay 400012. India The effect was studied of the steroid hormones, progesterone and estrogen. on tra~formation of human ~ripheral blood lymphocytes. A dose response curve using a concentration ranging from I to 501tg’ml was obtained for both

8.

STEROIDS

144.Foetal

adrenal function in diabetic pregnancy R.. KAL’PPILA. A., MOILANEN, K. and PAKARISEN, A.. Departments of Obstetrics and Gyneco-

TUINALA,

logy and Clinical land

Chemistry,

University

of Oulu.

Fin-

steroids. A S(r’,, inhibition of lymphocyte transformation was obtained with 25 pg of estrogen and 22~~ of progesterone. It was also observed that a concentration of IO&ml was inhibitory to lymphocyte transformation without being cytotoxic to the cells. This co~ntration was therefore used to study the sensitivity of lymphocytes to steroids. It was observed that in only I4 out of 21 samples studied to test the effect of progesterone was there an inhibition of lymphocyte proliferation. using whole blood culture (P > 0.05). whereas this inhibitory elect was more consistent when purified lymphocytes were used (P > 0.001). These results indicate that there is a marked variation in lymphocyte stimulation in human subjects to steroids. The effect is less marked when whole blood culture is used. Ex~rimental evidence suggests that other ceil types may have a regulatory effect on lymphocyte proliferation

IN PREGNANCY PZP significantly prolonged the survival of these transplants. The organ of origin for this protein has so far been controvenal. Results obtained from cell cultivation imply a multi organ site of synthesis including macrophagic cells from liver. spleen and other ret tculo-endot helial tissues.

of

Infants diabetic mothers have an increased risk of developing respiratory distress syndrome. which is due to the inhibition of surfactant production. Corticosteroids have a key role in the induction of surfactant production.

Recently we have found that infants of diabetic mothers have a relative low cortisol production l-6 days post parturn. The aim ol the present study was to investigate whether this impaired adrenal function could be detected antepartally. Amniotic fluid (AF) samples were drawn at the 36. 37”’ weeks from diabetic (N = 16) and control (N = 9) mothers. ACTH. cortisol and estriol were measured in AF by radioimmunoassay. In the diabetic group the mean ACTH ( k SD) was I80 f 97 ngl. corttsol 0.05 rf 0.01 pmol,‘l and estriol IS91 + 468 nmol:l. Respective control values were for ACTH 184 f 89 n&l. cortisol 0.04 i: 0.01 pmol,I and estriol 1093 f 425 nmolil. In diabetes the foetal adrenals seem to produce mare estrogens than in the control group which indicates higher activity of foetal zone (P < 0.01). No difference is. however. seen between cortisol levels indicating similar activity of adult zones. These results support previous observations or failed choline-phosphotransferase induction by cortisol due to increased insulin levels.

145. Pregnagey zone protein--as

immu~u~ive steroid regulated al 2-globulin DAMBER. M.-G..* LUNDGREN, E..t VON S~H~LXTZ. 6: and STIGBRASD, T..: *Department of Obstetrics and

Gynecology. the tDepartment of Pathology and the ZDepartment of Physiolog~al Chemistry, University of Ume& 90185 Umea. Sweden The pregnancy zone protein (PZP;pregnancy associated alpha, glycoproteinj is an alpha, macroglobulin (MW 3590009 which is known to increase during estrogen treatment and during pregnancy. PZP has no steroid-binding properties (estriol. oestradiol, oestrone. progesterone and cortisol). PZP has been suggested to be one of the nonspecific immunosuppressive factors operating in pregnancy. Immunosuppressive properties of this protein have been demonstrated in a variety of in cirro tests. Also in an in riro model using heterotopic transplantation of strongly histoincompatible mouse heart allograft. treatment with

146. Log-naima~ distribution of ovarian aad placental steroid values in early normal human pregnancy DISTLER, W.. ALBRETHT. H.. MORGFNSTERN,.I. and STOLLENWERK. U.. Department of Obstetrics and Gynecology. University of Dusseldorf. Dusseldorf. Federal Republic of Germany Concentrations of estradiol (El). progesterone (P). and I7

_hjdroxyprogesterone

(I 70H-PI were measured by ra~~oimmunoassay in individual serum samples obtained between the 4th and 17th week of pregnancy from a group of 304 women with normal gestations. Values obtained were statistically analysed in order to determine the arithmetic mean and the 95’)<, normal range ( i 2 standard devtations). It was noted hereby that the mean minus 2 SD. was either close to zero or negative. Therefore the data for each hormone were analysed for normality of the distrrbutions by the chi square test. For each hormone the chi Gquare test was significantly different (P < 0.001 J from the normal distribution. Sub~quently linear tra~formation by ranking analysis revealed the log-normal distribution of our data. Furthermore ranking analysis was used as graphical method to delineate a useful climcal range. which includes the mean and meaningful 95”;, confidence limits for Ez. P, and 17OH-P in early normal human pregnancies.

147. Clinical

usefulness of oestrogen-creatinine ratios in early morning samples of urine for ~nitori~ fetoplaceatal function RAO, L. G. S.. Bellshill Maternity Hospital, Bellshill. Lanarkshire.

Scotland

The clinical usefulness of oestrogen-creatinine ratios (mmol of total ~trogen~mol of creatmine, E:C) was investigated by measuring it on 75.000 early mornmg urine specimens from 5.600 abnormal pregnancies. Gestrogens were analysed by a fully automated Auto-Analyser method using the Kobe-lttrich reaction and creatinine by the alkaline picrate method. Our clinical experience is as follows: (1) no intra-uterine mortality (IUM) occurred in any pregnancy of more than 34 weeks of gestation when the