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Biomedical subjects

A Belanger

Publications and source records attributed to A Belanger.

At least 73 records · Page 4Linked to original sources
PubMed1985

Influence of high-density lipoprotein on estradiol stimulation of luteal steroidogenesis.

The aim of this investigation was to determine whether luteal cells utilize cholesterol derived from high-density lipoprotein (HDL) for steroidogenesis and whether estrogen enhances luteal utilization of exogenous sterol. Incubation of Day 15 corpora lutea (CL) with different doses of human HDL resulted in a dose-dependent increase in progesterone production. HDL in vitro enhanced the overall steroidogenic capacity. However, the percentage of increases in 17 alpha-hydroxyprogesterone, testosterone and estradiol were significantly less than that of progesterone. Day 12 hypophysectomized and hysterectomized pregnant rats were treated with either estradiol, testosterone or vehicle for 72 h. Serum pregnenolone and progesterone were markedly increased by the steroid treatment, yet in vitro production of progesterone by CL in all the groups was similar. However, in the presence of HDL in the media, only luteal tissues from steroid-treated rats increased their progesterone output. The reduced production of progesterone by luteal cells of vehicle-treated rats was not due to an accumulation of pregnenolone but to an overall reduction in exogenous sterol utilization. In summary, results of this investigation suggest 1) luteal cells of pregnant rats effectively utilize cholesterol from HDL for maximal steroidogenesis, and 2) estradiol may stimulate luteal steroidogenesis, at least in part, by affecting the incorporation or utilization of cholesterol from HDL into the cell.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Monoclonal antibodies for use with 125iodine-labeled radioligands in progesterone radioimmunoassay.

The interactions of heterologous and homologous 125I-iodinated radioligand with polyclonal and monoclonal antibodies directed against 11-hydroxyprogesterone hemisuccinate conjugated to bovine serum albumin were compared. Our data show that, with a polyclonal antibody, the use of the same bridge in the tracer and the antigen results in a low sensitivity while a heterologous tracer can decrease markedly the titer of antibody but increases the sensitivity of the radioimmunoassay. Due to the high specificity of monoclonal antibodies, the interaction with heterologous and homologous iodinated tracers is extremely variable from one antibody to another but the present results demonstrate that radioimmunoassays of very high sensitivity can be obtained with homologous and heterogeneous tracers. However, an appropriate tracer has to be selected to meet the requirement of such an assay.

Animals↗
PubMed1984

Metabolism of tritiated C19 steroids by Shionogi mouse mammary tumors.

In the present report, the metabolism of dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol and androstenedione has been studied in two different Shionogi tumors, one is androgen-dependent ("androgen sensitive") and grows in intact male mice and the other is apparently androgen-independent ("androgen insensitive") since the cells continue to grow in castrated antiandrogen (Flutamide) treated male animals. Our data clearly show that both the sensitive and insensitive tumors contain 3 beta-hydroxysteroid delta 5-delta 4 isomerase which causes the transformation of C19 steroids into potent androgenic steroids. However, the androgen sensitive tumor is able to convert 5-androstene-3 beta, 17 beta-diol into 2-hydroxyestrogens while the rate of conversion is extremely low in the insensitive tumor. Most interestingly, the production of 5 alpha-reduced steroids observed in both tissues was clearly higher in insensitive tumor homogenates.

Androgens↗
PubMed1984

Study of the direct effect of LHRH agonist on testicular 17-hydroxylase and 5 alpha-reductase activities in non-hypophysectomized adult rats treated with an anti-luteinizing hormone serum.

In order to study both direct and pituitary-mediated mechanisms of action of the LHRH analogue [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide upon testicular steroidogenesis in adult rat, we compared the effects of the agonist when administered alone or concomitantly with an anti-LH serum to non-hypophysectomized rats. Testicular steroid contents and in vitro progesterone and testosterone metabolism were determined. Anti-LH serum administration was able to prevent 5 alpha-reductase stimulation by the agonistic peptide, but not the inhibition of 17-hydroxylase activity. These data suggest that modulation of 17-hydroxylase involves both direct and pituitary-mediated processes, while 5 alpha-reductase stimulation is mainly if not only due to a pituitary-mediated mechanism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

Effect of acute ACTH administration on plasma steroid levels in the dog.

Production of adrenal steroids in intact and castrated dogs is stimulated acutely by ACTH. While the increase in plasma cortisol, 17-hydroxypregnenolone and 17-hydroxyprogesterone is not affected by castration, the increment of dehydroepiandrosterone is totally abolished. On the other hand, administration of 17-hydroxypregnenolone in adrenalectomized dogs caused an increase in plasma C-19 steroids such as dehydroepiandrosterone, androstenedione and testosterone indicating that this C-21 progestin in plasma is rapidly converted. The site of this conversion is likely the testis. Furthermore, acute hCG administration in adrenalectomized dogs resulted in a marked increase in the levels of plasma 17-hydroxypregnenolone and dehydroepiandrosterone. However, our data show an ACTH-induced rise in 5-androstene-3 beta. 17 beta-diol in intact and castrated dogs, thus suggesting that this steroid is a good parameter to assess in the stimulation of adrenal steroidogenesis by ACTH.

Adrenal Glands↗
PubMed1983

New approach in the treatment of prostate cancer: complete instead of partial withdrawal of androgens.

To completely eliminate androgens of both testicular and adrenal origin, 37 previously untreated patients with advanced (stages C or D) prostatic cancer received the combination therapy using an LHRH agonist (HOE-766) and a pure antiandrogen (RU-23908). The response criteria developed by the National Prostatic Cancer Project were used. A positive response (assessed by bone scan and/or serum prostatic acid phosphatase measured by radioimmunoassay was observed in 29 of the 30 cases who could be evaluated by these objective criteria (97%). The objective response was parallel to a rapid and marked improvement of the clinical signs and symptoms related to prostate cancer (prostatism, bone pain, and general well being). In marked contrast, the same combination therapy applied to patients previously treated with high doses of diethylstilbestrol (13 patients) showed a positive objective response in only 55% of cases. In 23 previously castrated patients showing relapse, an objective response was seen in only 25% of cases after neutralization of adrenal androgens by the antiandrogen. Previous treatment with chlorotrianisene (TACE) had no detectable effect on prostatic cancer and patients having previously received such treatment had a rate of positive response similar to previously untreated patients (five of five). In the previously untreated patients receiving the combination therapy, a 60% fall in serum prostatic acid phosphatase was observed as early as five days after starting treatment, at a time when the serum androgen concentration was 100% to 200% above control. Combined treatment with the pure antiandrogen completely prevents flare-up of the disease, a complication previously found in a significant proportion of patients treated with an LHRH agonist alone. The present data show that complete withdrawal of androgens by combined hormonal therapy with the LHRH agonist (or castration) and a pure antiandrogen leads to a positive objective response in more than 95% of cases as opposed to 60%-70% as reported by many groups using the previous partial hormonal therapy (castration or high doses of estrogens). Adrenal androgens are most likely responsible for this difference. The present study also shows that the proportion of androgen-sensitive cells decreases from more than 95% in untreated patients to 25% to 55% after previous partial hormonal therapy. Such data clearly indicate that the previous partial hormonal therapy exclusively aimed at neutralizing testicular androgens left 25% to 55% of cancer cells having a relatively low sensitivity to androgens in a hormonal milieu compatible with their continuous growth. No clinical or biochemical side effect could be detected except those related to reduced serum androgen levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1983

New hormonal treatment in cancer of the prostate: combined administration of an LHRH agonist and an antiandrogen.

At doses which have no or minimal inhibitory effect when administered alone, the LHRH agonist [D-Ser(TBU)6,des-Gly-NH10(2)] LHRH ethylamide (HOE-766) and the antiandrogen RU-23908 administered simultaneously cause a marked inhibition of ventral prostate and seminal vesicle weight after 5 months of treatment. The effect of the LHRH agonist is due to a blockage of the testicular steroidogenic pathway. The same LHRH agonist administered to adult men with cancer of the prostate causes a marked inhibition of serum testosterone and dihydrotestosterone to castration levels within 1-2 weeks. Administration of the pure antiandrogen to men with cancer of the prostate already receiving the LHRH agonist does not interfere with the LHRH agonist-induced blockage of androgen biosynthesis: Moreover, objective signs of remission of the disease were rapidly observed in 8 out of 10 patients. The ease of application of this new form of hormonal therapy which neutralizes androgens from all sources should facilitate its early administration and thus minimize the development of metastases and androgen-resistant cell clones.

Androgen Antagonists↗
PubMed1983

New hormonal therapy in prostate cancer: combined use of a pure antiandrogen and an LHRH agonist.

Treatment with an LHRH agonist (HOE-766) alone causes an almost complete blockage of testicular testosterone formation in rat and man. In order to neutralize androgens of adrenal origin, a pure antiandrogen (RU-23908) was given in combination with the LHRH agonist in the rat. At doses where each drug has no or minimal effect alone, prostate and seminal vesicle weight were reduced to 9 and 15% of control after 5 months of combined treatment, respectively. Among the species studied, man is the most sensitive to the inhibitory effect of treatment with LHRH agonists on testicular steroidogenesis. Near castration levels of serum testosterone and 5 alpha-dihydrotestosterone are obtained within 1-2 weeks of daily subcutaneous administration of the LHRH agonist [D-Ser(tbu)6, des-Gly-NH2(10)]LHRH ethylamide (HOE-766) in adult men with cancer of prostate. The decrease in serum androgen levels is accompanied by objective remission of the cancer in approximately 75% of cases. In a preliminary study where the LHRH agonist was administered in combination with the pure antiandrogen RU-23908, it was shown that the antiandrogen does not interfere with the LHRH-induced inhibition of serum androgen levels. The ease of application of this new form of hormonal therapy should permit its use at early stages of the disease and thus reduce the development of metastases and androgen-resistant cell clones.

Androgen Antagonists↗
PubMed1983

[New approach in the treatment of prostatic cancer: combined use of a LHRH agonist and an androgen antagonist].

Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high doses of estrogens. These two approaches cause a temporary improvement in 60 to 70% of advanced prostatic cancer. However, castration is not always well accepted and high doses of estrogens are frequently accompanied by lethal cardiovascular side effects. Following our observation that treatment with LHRH agonists causes a blockage in the biosynthesis of testosterone by the testis accompanied by a marked reduction in prostatic weight in the rat, the possibility was opened for a new approach in the treatment of prostatic cancer. Fortunately, among all species studied, man is the most sensitive to the inhibitory effect of LHRH agonists on testicular androgen biosynthesis and near-medical castration can be easily achieved without secondary effects other than those related to low androgen levels. Following long-term studies in the rat which have shown that the inhibitory effect of LHRH agonists is markedly potentiated by simultaneous administration of a pure antiandrogen, a study using the LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide (HOE-766) and the pure antiandrogen RU-23908 was performed in men with advanced prostatic cancer. The combined treatment with the LHRH agonist and the antiandrogen in 37 patients not previously treated caused a positive objective response in 97% of cases while, previously, partial hormonal treatment achieved through castration or high doses of estrogens caused a positive response in 60 to 70% of patients. The serum levels of prostatic acid phosphatase (PAP) were decreased to 40% of control as early as four days after starting combined hormonal therapy. By contrast, in patients previously treated with estrogens or castrated, complete neutralization of adrenal androgens by the antiandrogen led to a much lower rate of positive response ranging from 25 to 55%. In patients previously treated, there is thus a predominance of tumor cells insensitive to androgens. An additional important finding in this study is that the administration of the antiandrogen prevents the flare-up of the disease frequently observed when LHRH agonists are administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1982

Best estimate of lifetime psychiatric diagnosis: a methodological study.

It is important for genetic, epidemiologic, and nosological studies to determine accurate rates of lifetime psychiatric diagnoses in patient and nonpatient populations. As part of a case-control family study of major depression, lifetime psychiatric diagnoses were made for 1,878 individuals. Sources of information used in making diagnostic estimates included direct interview, medical records, and family history data systematically obtained from relatives. Diagnostic estimates were made by trained interviewers, experienced clinicians, and by computer program. The results indicate that it is possible to make lifetime best estimate diagnoses reliably among both interviewed and noninterviewed individuals for most diagnostic categories and that diagnoses based on interview data alone are an adequate substitute for best estimate diagnoses based on all available information in a limited number of diagnostic categories.

Computers↗
PubMed1982

Comparative effects of LHRH agonist and ovine LH administration on testicular steroidogenesis in intact adult rat.

In order to better understand the effects of LHRH administration on testicular function in adult rat, we compared the inhibitory effects of LH and LHRH analogue [D-Ser-(TBU)6, des-Gly-NH2(10)]LHRH ethylamide upon testicular steroidogenesis and LH, FSH and prolactin receptor contents. Administration of LH as well as LHRH analogue resulted in a marked decrease of LH receptor levels, accompanied by a blockage at the level of 17-hydroxylase activity. We have been able to demonstrate that multiple LH administration can achieve a testicular desensitization comparable to that observed after LHRH agonist treatment.

Animals↗
PubMed1982

Comparison of the family history method to direct interview. Factors affecting the diagnosis of depression.

This study compares information on the diagnosis of depression obtained by family history reports with the formation obtained by direct interview. Reports were obtained from family members on the psychiatric status of 696 individuals for whom direct SADS-L interviews were also available. The effects on family history reports of subjects characteristics, treatment status, age of onset of depression, and endogenous symptoms were examined. Sensitivity and specificity for family history reports on the specific symptoms of depression are also reported. The specificity of family history reports for the diagnosis of depression was consistently high but sensitivity varied as a function of subject and illness characteristics. Sensitivity was somewhat higher for females than males and appreciably higher for probands than for their first-degree relatives and spouses. Sensitivity was increased whenever treatment, hospitalization or endogenous symptoms were present in the subject, indicating that family history reports are most accurate for detecting the severest cases of depression. Finally, the symptoms of depression that are least accurately reported by relatives are identified and suggestions for modifying the family history criteria for depression are proposed.

Adult↗
PubMed1982

Effects of chronic treatment with a potent luteinizing hormone releasing hormone agonist on serum luteinizing hormone and steroid levels in the male rhesus monkey.

The effects of chronic administration of [D-Ser(TBU)6, des-Gly-NH2 10]LHRH ethylamide (Buserelin, Hoe 766) on plasma LH, pregnenolone, 17-hydroxyprogesterone, testosterone and dihydrotestosterone levels were studied in a nonhuman primate species, the rhesus monkey. After 1 week of daily administration of 25 micrograms of Hoe 766, the LH response measured after 3 h and 7 h is markedly inhibited when compared to the previous week's response and a slight decrease in basal LH levels is observed. A small rise of plasma LH is, however, always seen 3 h after administration of the peptide during the whole treatment period. Serum testosterone levels display a rapid stimulation from 7 to 35 ng/ml 3 h after the first administration of Buserelin and increase progressively up to at least 12 h (44 ng/ml). Plasma concentrations of 17-hydroxyprogesterone increase more slowly from 2.0 to 3.4 ng/ml during the first 3 h and reach 9.5 ng/ml 9 h later. By contrast, there are no or minimal changes or serum pregnenolone and dihydrotestosterone levels following the first injection of Hoe 766 and during the course of the study. While the acute testosterone response to Buserelin measured at 3 h is not affected in up to seven weeks of treatment with the peptide, the duration of testosterone and 17-hydroxyprogesterone response measured at later time intervals (7 h, 12 h) is decreased to 20% to 50% of control. The data suggest that the testicular steroidogenic pathway in rhesus monkeys retain its ability to respond to LH stimulation during treatment with the LHRH agonist while the basal testosterone levels are reduced. The close correlation observed between reduced serum LH and testosterone concentrations suggest that pituitary desensitization is the main factor responsible for the partial inhibition of basal testosterone concentration in rhesus monkeys.

Animals↗
PubMed1982

New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen.

In order to block the influence of androgens from all sources on the growth of prostatic cancer, we have used a new hormonal therapy based on medical castration achieved with the potent LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide (HOE-766) combined with the administration of a pure antiandrogen that neutralizes the action of adrenal androgens as well as those still secreted in low amounts by the testis during LHRH agonist treatment. This study was performed in ten patients with advanced prostatic carcinoma (9 at stage D2 and one at stage C). Bone pain, prostatism and general well-being were 60 to 90% improved within one month after starting treatment in all patients. After 2 months of treatment, minimal bone pain remained only in one patient who was originally bedridden. Bone scanning showed a 70 to 90% decrease in uptake after 3 to 5 months of treatment in the patients studied. Acid phosphatase levels were 60 to 90% reduced after 2 months of treatment in 3 out of the 4 patients who had elevated levels before therapy. Marked objective and subjective improvement was thus rapidly observed in 9 out of 10 patients treated with the combined therapy, while, in the other patient at stage C, subjective improvement could be documented. Although preliminary, this study indicates that a combined hormonal therapy which neutralizes all androgenic influences on peripheral tissues is of potential benefit in prostatic cancer. Moreover, the ease of application as well as the lack of secondary effects of the present approach should make possible its use early in the disease and should thus minimize the development of metastases and androgen-resistant cell clones. Randomized prospective studies on this potentially beneficial therapy are warranted.

Adenocarcinoma↗
PubMed1982

Primary hyperparathyroidism in children.

Primary hyperparathyroidism is rare in children. This report describes a 15-year-old boy who had an intrathymic chief cell adenoma. The literature related to this condition in neonates and children is reviewed. Neonatal hyperparathyroidism differs from hyperparathyroidism in children. The severity of symptoms and osseous lesions, genetic inheritance in many, pathological changes in the parathyroid glands and the need for more extensive treatment in neonates and infants indicate that primary hyperparathyroidism in these patients should be considered as a different entity from that occurring in older children.

Adenoma↗