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R B Thau

Publications and source records attributed to R B Thau.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗
PubMed1983

Characterization of a human anti-hCG antiserum: a proposed standard for laboratories involved with the development of hCG vaccines.

An antiserum (PC-81-1) was obtained from a man who developed antibodies against hCG during treatment for hypogonadism. The antiserum was unique in that its affinity for hCG was high (greater than 10(-10) M(-1] and its cross-reaction with hLH and the hCG-subunits was only 1-12.5% and 0.01%, respectively, of intact hCG. We propose that this human antiserum be used as a laboratory standard by investigators who are developing vaccines directed against hCG. The use of this standard in the proposed protocol will permit comparison of titers between laboratories. Lyophilized samples of antiserum PC-81-1 are available on request from the Population Council.

Antibodies↗
PubMed1983

Influence of a levonorgestrel-containing contraceptive vaginal ring on plasma lipids and lipoproteins in cynomolgus monkeys.

The effect of a contraceptive vaginal ring (CVR) containing levonorgestrel on plasma lipid and lipoprotein concentrations and characteristics was assessed in ten cynomolgus monkeys. The animals were fed a diet similar to the average American diet in fat (40% of calories) and cholesterol (0.2 mg/kcal) content. The objective of this study was to determine if changes in lipids and lipoproteins caused by progestogen administration parallel those seen in human females. A parallel pattern would recommend the cynomolgus monkey as a model for studying the effects of progestogens on the atherosclerotic process. Treatment with the CVR resulted in significant decreases in total plasma, VLDL + ILDL + LDL, and HDL cholesterol concentrations and a decrease in the percentage of HDL2 in total HDL. Plasma triglyceride concentrations were low throughout the study and consistent effects of the CVR were not seen. CVR treatment resulted in increases in TPC:HDL-C ratios and in the flotation rate of the LDL particle. The patterns of effects on HDL cholesterol, total plasma cholesterol, and HDL2 concentrations were similar to the progestogen-induced changes observed in human plasma lipids and lipoproteins. Based on these effects, the cynomolgus monkey appears to be a suitable model for the study of progestogen-induced changes in plasma lipids and lipoproteins and their consequent influences on coronary artery atherosclerosis.

Animals↗
PubMed1983

Characterizations of anti-oLH beta antibodies acting as contraceptives in rhesus monkeys. II. In vivo neutralizing ability for gonadotropic hormones.

63 female rhesus monkeys were actively immunized against the beta-subunit of ovine luteinizing hormone (oLH beta). 75% of these monkeys developed antibodies which were sufficiently high to induce infertility. We report here the in vivo neutralizing potencies of anti-oLH beta antisera from 14 monkeys and the correlation between in vitro and in vivo properties of the antibodies. Anti-oLH beta sera neutralized the biological activity (stimulation of testosterone production in male mice) of both hCG and rhCG. The correlation between antibody titers and neutralizing potency of hCG action of the antisera was significant. rhCG-induced testosterone production was inhibited more effectively than that induced by hCG. There was no correlation between binding affinity to hCG in vitro and neutralizing activity. Neutralizing activities correlated well with binding capacities, suggesting that the number of binding sites of the antibody population may play an important role in the mechanism of neutralization. In rhesus monkeys that were effectively immunized against pregnancy circulating oLH beta antisera did induce shortened luteal phases and impaired luteal function. Successful application of oLH beta as an antigen for contraception in humans may depend on relative cross-reactions of hLH and hCG with anti-oLH beta sera and on a neutralizing capability very similar to the one found in rhesus monkeys.

Animals↗
PubMed1983

Effects of long-term immunization against the beta-subunit of ovine luteinizing hormone on circulating immune complex formation and on arterial changes in rhesus monkeys.

A major safety issue of contraceptive methods based on long-term immunization is the possible effect of circulating immune complexes (CIC) on the arterial wall. We have measured CIC's in 24 monkeys, immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), emulsified with Freund's complete adjuvant, and in 7 nonimmunized controls by Raji assay, Clq assay, and an assay for rheumatoid factor. Eleven of the 24 immunized monkeys had CIC concentrations that were more than two standard deviations above the mean for controls in at least one of the assays. There was no correlation between antibody titer and CIC. Nine immunized and eight control animals on low-fat diets were killed to evaluate the effects of immunization on the artery wall. The cross-sectional intimal area was measured at several sites from projected microscopic images using a sonic digitizer. No statistically significant differences between test and control groups were found. However, when we compared the upper half of the distribution of test and control animals, we found that the mean intimal area of the thoracic aorta of immunized monkeys was twice that of controls and that that of the abdominal aorta was three times as large. These data indicate that long-term immunization against oLH beta induced CIC's in rhesus monkeys. Small increases in the intimal area were found in about half of the immunized animals. The results of this study suggest the need for a larger, more definitive study in which the diet is manipulated so that plasma lipids mimic those of human females in Western society.

Animals↗
PubMed1983

Bioassay for anti-chorionic gonadotrophin sera.

The method for a rapid bioassay for the neutralizing activities of antichorionic gonadotrophin sera is based on the inhibition of the increase in plasma testosterone concentrations in male mice after the injection of antiserum and human chorionic gonadotrophin (hCG). The antisera were obtained from rhesus monkeys immunized against the beta-subunit of ovine luteinizing hormone (oLH beta). The anti-oLH beta sera neutralized the hCG-induced testosterone stimulation. A dose-response relationship for neutralization was found between 25 and 200 microliters antiserum. Anti-hCG sera raised in human, chimpanzee and rabbit also neutralized the biological activity of hCG. The major advantage of this method is that the single injection of antiserum given before hCG administration leads to the hormone-antibody reaction in vivo.

Aging↗
PubMed1982

Impaired steroidogenesis in the luteal phase of the reproductive cycle and during pregnancy in rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone.

Monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLH beta) develop antibodies which cross react with rhesus chorionic gonadotropin (rhCG) and luteinizing hormone (rhLH). Immunization causes shortened menstrual cycles and reduced fertility. Fertility can be restored by administration of medroxyprogesterone acetate (MPA) during the first 5 weeks of pregnancy. In the present study, we have measured the effects of circulating oLH beta-antibodies on peripheral estradiol, progesterone and 17 alpha OH-progesterone (17OH-P) concentrations throughout the menstrual cycle and during gestation in monkeys which became pregnant following MPA-treatment. Progesterone concentrations were markedly reduced during the luteal phase in cycling animals and the luteal phase of the cycle was significantly shorter as compared to non-immunized controls. Concentrations of estradiol and 17OH-P in the peripheral circulation were not affected by the oLH beta-antibodies. In immunized monkeys which became pregnant following MPA-treatment, progesterone and 17OH-P levels were consistently lower and estradiol concentrations were increased during the second and third trimesters. Our results show that circulating antibodies to oLH beta have multiple endocrinological effects. Corpus luteum function is impaired in cycling monkeys and during the early part of pregnancy. In addition, the pattern of steroid secretion remains abnormal in pregnant monkeys even after the luteal-placental shift.

Animals↗
PubMed1982

Characterization of anti oLH beta-antibodies acting as contraceptives in rhesus monkeys. I. In vitro binding properties.

Female monkeys actively immunized with oLHbeta are infertile when circulation antibody titers become sufficiently high to bind 30% of an iodinated hCG standard. We report here the extensive characterization of the oLHbeta antibodies. Their binding affinity and capacity for human and rhesus gonadotropins were determined. The affinity was high (Ka - 10(9) M-1) and was similar for high, medium and low titer antisera. In contrast, the binding capacity for hCG correlated well with antibody titers (n = 18, r = 0.888, P less than 0.001) and ranged from 0.09 to 8.3 x 10(-7)M. Column chromatographic analysis showed that anti-oLHbeta was mostly IgG. A temporal increase of affinity ('maturation') after booster was absent in the majority of monkeys. Cross-reaction between hCG and hLH as well as rhCG and rhLH was high. The latter, however, did not interfere with regular cycles and ovulation, suggesting that oLHbeta may be a useful antigen for human contraception.

Animals↗
PubMed1981

Human chorionic gonadotropin maintains plasma progesterone at pregnancy levels in rhesus monkeys.

Peripheral plasma progesterone (P) levels in the rhesus monkey remain relatively constant both during the latter half of pregnancy and for long periods after fetectomy (removal of the fetus with the placenta left in situ) or ovariectomy. The constancy is maintained despite what appears to be reciprocal changes in the relative contributions of ovary and placenta. Placental regulation of the corpus luteum is likely, but it is not known if the corpus luteum responds to a gonadotropic stimulus in the later stages of pregnancy. In this study, we have investigated the effects of hCG administration in postdelivery monkeys (normally pregnant, fetectomized, ovariectomized and sham ovariectomized animals) and have determined if hCG administration maintains plasma P at pregnancy levels. hCG maintained P at pregnancy levels after surgical removal of the conceptus near term in both normally pregnant and previously fetectomized monkeys over a 7-day treatment period. hCG treatment after normal delivery maintained P levels in sham-ovariectomized but not in ovariectomized monkeys over an 8-day treatment period. The magnitude of the response to hCG declines over the treatment period in all groups except fetectomized monkeys, although hCG levels in the peripheral plasma are quite constant. These results indicate that the ovary of late pregnancy is fully capable of producing P at normal values and is responsive to this gonadotropin.

Animals↗
PubMed1980

The mechanism of action of an antifertility vaccine in the rhesus monkey: reversal of the effects of antisera to the beta-subunit of ovine luteinizing hormone by medroxyprogesterone acetate.

Active immunization of female rhesus monkeys with the beta-subunit of ovine luteinizing hormone )oLH beta) significantly reduced their fertility. To determine whether the major action of the vaccine was interruption of pregnancy, by suppression of "corpus luteum rescue," or inhibition of ovulation, we administered the progestational agent medroxyprogesterone acetate (MPA) from day 4 through day 40 after mating. In the untreated immunized group, the pregnancy rate was significantly below that of control monkeys. MPA treatment restored the fertility rate of immunized animals to that of the control group. These results strongly support the assumption that the antifertility action of antibodies of oLH beta is due to prevention of corpus luteum rescue. Whether the lack of corpus luteum rescue resulted because of neutralization of rhesus monkey chorionic gonadotropin or from a defective corpus luteum, as is found in animals with short luteal phases, cannot be determined from these studies. The successful reversal of the antifertility effect, however, suggests that the circulating antibodies do not interfere with normal ovulation or with the normal development and implantation of the blastocyst.

Animals↗
PubMed1979

Observations on progesterone production and clearance in normal pregnant and fetectomized rhesus monkeys (Macaca mulatta).

The metabolic clearance rate (MCR) and production rate (PR) of progesterone were measured in rhesus monkeys both before and during intravenous infusion of progesterone at rates which approximately doubled or tripled the peripheral plasma levels. The monkeys were normally pregnant or fetectomized and were studied during the second half of pregnancy. Raising the peripheral plasma levels did not significantly after the MCR or the PR of progesterone. We conclude that peripheral progesterone levels are not the factor which controls the PR of progesterone in rhesus monkeys.

Animals↗
PubMed1979

Effect of the fetal placenta and of a rabbit pituitary extract on plasma progesterone in fetectomized rabbits.

When fetuses and placentas were removed on Day 18 in normal pregnant rabbits, plasma progesterone levels declined rapidly to non-pregnant values within 48 h. This decline was largely prevented if only fetectomy was performed, leaving the placentas in situ, but not when the fetal components of the placentas were also removed. These results suggested that ovarian progesterone production was dependent upon trophic influences emanating from the fetal portions of the placentas. Ovarian progesterone production was maintained by an extract of rabbit pituitaries for at least 72 h after removal of fetuses and placentas.

Animals↗
PubMed1979

Effects of immunization with the beta-subunit of ovine luteinizing hormone on corpus luteum function in the rhesus monkey.

Rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLHbeta) developed circulating antibodies which cross-reacted strongly with rhesus monkey chorionic gonadotropin. Normal ovulatory cycles continued, but the fertility of immunized monkeys as compared with that of controls was significantly reduced. Thus, the rhesus monkey represented a useful animal model for the study of certain aspects of an "antifertility vaccine." We investigated the effects of circulating antibodies to oLHbeta on corpus luteum function by measuring production rates (PRs) and peripheral concentrations of progesterone during the luteal phase of the menstrual cycle. Both parameters were significantly lower in immunized animals than in control animals. The length of the menstrual cycle was also significantly reduced. Progesterone PRs were also determined on days 10 and 15 after mating to test the assumption that the antifertility vaccine prevents pregnancy by interfering with "corpus luteum rescue" (the increase in PRs of progesterone usually occurring on day 15 after mating in fertilized animals). PRs increased from days 10 to 15 in pregnant controls, were unchanged in nonpregnant controls, and were significantly lower on day 15 in immunized monkeys as compared with nonpregnant and pregnant controls. These results suggest that "corpus luteum rescue" is suppressed in immunized animals.

Animals↗
PubMed1975

Metabolic clearance rates (MCR) and production rates (PR) plasma progesterone in pregnant and pseudopregnant rabbits.

Our studies were designed to determine whether changing peripheral progesterone levels in rabbits reflected changing metabolic clearance rates (MCR) or changing production rates (PR), or both. Plasma progesterone concentrations rise from nonpregnancy levels to peak values at the end of the first third of gestation and at midpseudopregnancy. In the pregnant rabbit, these decline slowly during the second third of gestation and then more rapidly until near nonpregnancy values are reached at term. Progesterone levels decline sharply during the second half of pseudopregnancy. During pregnancy and pseudopregnancy, we found only small variations in MCRs which cannot account for the approximately 10-fold increase in plasma progesterone concentrations. The increases can, however, be accounted for by changes in PRs which rose sharply after conception of hCG injection to 14-fold the nonpregnancy level on day 16 of gestation and 11-fold on day 7 of pseudopregnancy. These results indicate that changes in ovarian PRs are the major factor for the variations in peripheral progesterone levels during pregnancy and pseudopregnancy. The rabbit differs in this respect from the guinea pig, in which changing progesterone concentrations during pregnancy were shown to reflect sharply reduced MCRs. After a single injection of progesterone in 20-day pregnant rabbits, the disappearance of the steroid from the circulation consisted of two components; an initial phase during which progesterone disappeared rapidly (t1/2 = 2.4 +/- 0.2 min) followed by a slower rate of disappearance (t1/2 = 21.5 +/- 2.2 min).

Animals↗
PubMedDate not supplied

Reversal of testicular function after prolonged suppression with an LHRH agonist in rhesus monkeys.

Using subcutaneously implanted osmotic pumps, four male rhesus monkeys were continuously infused for 18 months with 100 micrograms/day of [(imBzl)-D-His6-Pro9-NEt]-LHRH (LHRH-A), a potent agonist of LHRH. After an initial increase, serum testosterone levels declined to 10% of pretreatment levels in three monkeys and the response to electroejaculation was lost. There was a decrease in testicular volume. Androgen replacement in the form of subcutaneous SILASTIC implants releasing 7 alpha-methyl-19-nor-testosterone acetate led to a restoration of ejaculatory response and the electroejaculates were devoid of spermatozoa. Under this treatment regimen (100 micrograms LHRH-A + 100 micrograms androgen daily), azoospermia was essentially maintained in the three monkeys for about 8 months. Withdrawal of LHRH-A and androgen treatment led to a complete restoration of testicular function. Serum testosterone returned to control levels and spermatozoa reappeared in the ejaculates with sperm counts reaching the normal range. Testicular volumes showed a gradual increase. These results indicate that continuous administration of an LHRH agonist together with an androgen can induce an extended period of azoospermia in rhesus monkeys. These results also show that after prolonged suppression (more than one year) of testicular function complete recovery occurs after cessation of treatment.

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