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Biomedical subjects

R Thau

Publications and source records attributed to R Thau.

15 recordsLinked to original sources
PubMed1992

Anti-LHRH and anti-pituitary gonadotropin vaccines: their development and clinical applications.

Active immunization against hormones involved in the regulation of reproduction is a promising approach to immunocontraception. The hypothalamic peptide, LHRH, controls the synthesis and release of the pituitary gonadotropins, LH and FSH, which regulate gonadal steroidogenesis, sperm production, follicular development and ovulation. Immunizing female primates against LHRH or LH induces infertility, but also disrupts the menstrual cycle. Immunization against the beta subunit of the placental hormone, chorionic gonadotropin (hCG), or its fragment prevents pregnancy without interfering with menstrual cycles or ovulation. hCG vaccines have reached the stage of clinical trials. FSH and LHRH have been tested for immunocontraception in male primates. While active as well as passive immunization against FSH reduced spermatogenesis severely, azoospermia could not be achieved consistently. Immunization against LHRH effectively suppressed spermatogenesis in rats and rabbits. Normal sexual behaviour was maintained by concomitant androgen administration. Fertility was restored when antibody titres declined and no adverse effects were observed. A number of LHRH vaccine preparations are being tested in men in several countries, including the United States. Since the LHRH vaccine reduces serum testosterone levels the first clinical studies involve men with prostate cancer. These trials will be followed by immunization of normal men if the antibody response is sufficient and no adverse effects are observed.

Animals↗
PubMed1990

Radioimmunoassay of 7 alpha-methyl-19-nortestosterone and investigation of its pharmacokinetics in animals.

A method for the measurement of 7 alpha-methyl-19-nortestosterone (7MENT) in serum/plasma by radioimmunoassay (RIA) is described. The antiserum, raised against 7 alpha-methyl-19-nortestosterone-3-O-oxime-bovine serum albumin, had a low titer (final dilution = 1:4500) and low affinity (Ka = 1.17 x 10(9) l/mol) but showed little or no cross-reactivity with several of the steroids tested. The sensitivity of the RIA was 28.2 pg/ml and the mean recovery of added cold steroid was 86 to 100%. Intra- and inter-assay coefficients of variation ranged from 4.3 to 7.3% and 7.3 to 8.4%, respectively. This RIA was used to follow plasma 7MENT levels after a single i.v. injection of the steroid in rats and rabbits. The metabolic clearance rates (MCR) of 7MENT as determined from the plasma disappearance curve for rats and rabbits were 50 l/day and 336 l/day, respectively. The MCR of 7MENT in rats and rabbits lies in the same range as for testosterone. When compared to other nortestosterone derivatives such as norethisterone, 7MENT is metabolized relatively faster.

Animals↗
PubMed1989

Effects of long-term immunization against LHRH and androgen treatment on gonadal function.

The possibility of immunological suppression of spermatogenesis while normal libido is maintained by exogenous androgen supplementation was tested in male rats. Neither short- nor long-term treatment with androgen (testosterone-17-trans-4-N-butyl-cyclohexane carboxylate) alone influenced fertility. Active immunization against LHRH administered simultaneously with exogenous androgen supplement caused infertility in 100% of the tested animals, all of which displayed normal sexual behavior. The atrophy of the testes and accessory sex organs was reversible.

Animals↗
PubMed1988

Conditional task-related responses in monkey dorsomedial frontal cortex.

Dorsomedial frontal cortex (DMFC) was studied in monkeys trained to make visually guided eye or arm movements. Portions of DMFC are involved in the execution of learned, goal-directed behaviors. Many neurons discharge with both eye and hand movements as well as when motor responses are withheld, provided these behaviors are related to the successful execution of the learned task. Similar movements, when carried out at times unrelated to the task, are not accompanied by neuronal activity. Electrical microstimulation produces either arrest of task-related, but not task-unrelated motor acts, or triggers task-related movements. The nature of stimulation elicited responses depends on the task the animal has been trained on and is altered by new training.

Animals↗
PubMed1988

Antagonists of luteinizing hormone releasing hormone bind to rat mast cells and induce histamine release.

It was reported previously that administration of certain synthetic antagonists of LHRH to rats produced allergy-like symptoms that were attributed to their histamine releasing action. In the present study the interaction of LHRH analogs with rat peritoneal mast cells was investigated in vitro. Potent antagonists of LHRH showed strong in vitro histamine releasing activity from rat peritoneal mast cells. Membrane preparations of rat pituitary glands showed specific binding of radioiodinated LHRH antagonist as well as LHRH agonist. However, rat peritoneal mast cells and membrane preparations from those cells bound antagonist but not the agonist. Furthermore, the LHRH antagonist did not bind to membranes prepared from tissues such as prostate, liver, kidney, and brain. Competitive displacement curves of the [125I]-antagonist with different LHRH analogs showed that the ability of the analogs to compete for binding sites on mast cells was related to their histamine releasing activity. We conclude that histamine release from rat mast cells induced by LHRH analogs is mediated by specific binding of the active peptides to cell membranes. Furthermore, using rat mast cells, the binding assay in conjunction with histamine releasing assay may be utilized to predict the in vivo histamine releasing potential of new LHRH peptides which are of clinical importance.

Animals↗
PubMed1988

Androgen binding protein in serum, testis and epididymis following treatment with the Leydig cell cytotoxic agent, ethylene dimethanesulphonate.

Androgen binding protein (ABP) was measured in the serum, testes and epididymides of adult male rats after treatment with ethylene dimethanesulphonate (EDS), which has direct cytotoxic effects on Leydig cells and secondarily affects sperm production. Serum ABP increased to a maximum 7 days after treatment and remained elevated for most of the 63 days of observation. The ABP content of both the epididymides and testes declined and were low between 14 days and 21 days following treatment. By contrast, the concentration of ABP in these tissues was maintained after EDS treatment and was sometimes elevated. This divergence between ABP content and concentration was due to atrophy of the testes and epididymides after the decline in androgen secretion. The changes in serum and tissue ABP levels after EDS occurred earlier than those observed in adult hypophysectomized animals, possibly due to local paracrine influences that are lost secondarily to destruction of the Leydig cells. Testicular testosterone did not parallel ABP content as it fell dramatically 2 days after EDS and remained low for about 21 days before returning to near control values after 63 days. Testicular and epididymal sperm heads decreased in number after EDS, but were not clearly associated with the changes in ABP. The results confirm that androgens are important for the production of ABP and for the partitioning of this protein between the blood and the lumen of the reproductive tract.

Androgen-Binding Protein↗
PubMed1984

Do testicular opiates regulate Leydig cell function?

beta-Endorphin is believed to be synthesized in testicular Leydig cells. To gain more information about the role of this and other endogenous opioid peptides in the testis, opiate antagonists (naloxone and nalmefene, 100 micrograms/testis) were administered intratesticularly to hemicastrated adult rats. Leydig cell function was evaluated by measurement of serum testosterone and testosterone production in vitro. Estimation of androgen binding protein (rABP) was used as an index of Sertoli cell function. Serum testosterone was reduced significantly by intratesticular administration of naloxone and nalmefene in treated animals. Systemic administration of these antagonists had no effect at the doses used. Testes from treated animals incubated in vitro with or without hCG produced significantly less testosterone than vehicle-treated control testes. Hemicastration reduced rABP synthesis and secretion; however, treatment with opiate antagonists did not alter the amount of this protein in the serum or epididymides of these rats. These observations suggest that endogenous testicular opiates modulate testosterone secretion by Leydig cells.

Androgen-Binding Protein↗
PubMed1982

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Amygdala↗
PubMed1975

Ovarian and placental origins of plasma progesterone following fetectomy in monkeys (Macaca mulatta).

Fetectomy, either alone or combined with ovariectomy, was performed in 17 monkeys. Following fetectomy alone in 8 animals, progesterone values were maintained at normal pregnancy levels (1.0 ng/cc plasma or more), until expulsion of the placenta, which frequently occurred at a time well past normal term. Values declining toward but not reaching the nonpregnancy range were observed in some animals in the 2 to 6 weeks preceding expulsion; no similar decline occurs preceding normal labor. In all cases, after the placenta was expelled, progesterone values fell below 1 ng/cc plasma within 2 days. When ovariectomy was superimposed on 3 animals previously fetectomized, plasma progesterone values fell abruptly to nonpregnancy levels, and the placenta was expelled in an average of 6.3 days. The source of the progesterone in these fetectomized animals was, therefore, the ovaries, not the placenta damaged by a preceding fetectomy. However, the ovarian progesterone production after fetectomy was dependent on the continued presence of the placenta. In 6 animals following ovariectomy, and with an intact fetus and placenta, plasma progesterone levels were usually maintained at normal pregnancy levels. When fetectomy was superimposed in these animals with a preceding ovariectomy, plasma progesterone levels fell into the nonpregnancy range in an average of 4.8 days, and placental expulsion occurred after an average of 30.8 days. We believe this reflected a deteriorating ability of the fetectomized placenta to produce progesterone, which was capable only transiently of maintaining plasma values, but later of exerting sufficient local effect to maintain uterine quiescence for a longer time.

Animals↗
PubMedDate not supplied

The effects of the indazole carboxylic acid derivative, tolnidamine, on testicular function: I. Early changes in androgen binding protein secretion in the rat.

The indazole carboxylic acid derivative, tolnidamine, has marked antispermatogenic activity in several animal species. In this study, we assessed the effect of tolnidamine on rat Sertoli cell function both in vivo and in vitro, using androgen binding protein (rABP) as a marker. Groups of six male rats were killed 2, 4, 8, 16, 32, 64 hours and 5, 8, and 12 days following tolnidamine administration (250 mg/kg by oral gavage). There was a progressive reduction in both testicular and epididymal weights. Serum FSH levels did not change and LH showed a transient increase between 64 hours and 8 days. Except for an initial increase at 2 hours, there were no changes in serum testosterone. Epididymal rABP concentration and content declined as early as 8 hours, with the lowest values occurring at 5 and 12 days. By 16 hours, there was an increase in testicular rABP, which was also evident at 8 days and 12 days. Within 16 hours after tolnidamine, there was a rise in serum rABP, which persisted until the end of the experiment. When another indazole carboxylic acid derivative, lonidamine, was administered (250 mg/kg), similar changes were evident in epididymal and serum rABP at 32 hours, but the rapid decrease in testicular rABP suggested a different mechanism of action. In another experiment, single oral doses of tolnidamine (50, 100, 250, and 500 mg/kg) were administered to other groups of rats and the animals were killed after 24 hours and 5 days. With increasing doses of tolnidamine, there was a reduction in epididymal rABP concomitant with an increase in testis and serum rABP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Binding Protein↗