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Biomedical subjects

M Ben-David

Publications and source records attributed to M Ben-David.

At least 19 recordsLinked to original sources

Prolactin and luteinizing hormone-releasing hormone receptors in human benign prostatic hyperplasia and prostate cancer.

Using a sensitive micromethod for the determination of prolactin (PRL) binding sites based on 125I-human PRL ligand, PRL receptor levels in specimens of benign prostatic hyperplasia (BPH) and human prostate cancer were estimated by the one-point assay system. Ten of 19 BPH specimens (53%), showed significant PRL binding, four being in the 9-12 fmol/mg range. All ten of these cases had an histological diagnosis of nodular glandular hyperplasia. Of ten adenocarcinomas examined, four samples (40%) exhibited positive PRL binding, the highest receptor levels being 10.2 fmol/mg protein. To characterize the receptors from BPH membranes, samples were then separately pooled according to the results obtained in one-point assays. In the PRL-negative pool no displacement could be detected. In the PRL-positive pool, the Scatchard analysis revealed one class of receptors with an average affinity Kd = 1.1 X 10(-9) M and capacity Bmax = 287 fmol/mg protein. In the prostate cancer specimens, luteinizing hormone-releasing hormone receptors with a high affinity and a low capacity were also found. The results indicate the presence of prolactin receptors in prostate cancer and in BPH. The clinical implications of such findings are not clear, but it is possible that a certain proportion of BPH and prostate cancers might be in part PRL dependent. Further studies are necessary to ascertain this hypothesis in an attempt to improve the treatment of BPH and prostate cancer.

Gonadotropin-Releasing Hormone

Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.

Adenocarcinoma

First trimester bleeding in clinical IVF pregnancies.

First trimester bleeding has been investigated in 72 pregnant women undergoing in-vitro fertilization and embryo transfer and was compared to 70 pregnant patients in whom ovulation was induced, in addition to 70 spontaneous pregnancies. Abortion rates did not differ significantly between the first two groups but were significantly higher in comparison to normal pregnancies. Furthermore, among IVF pregnancies that continued, a high incidence of first trimester bleeding occurred (P less than 0.01). This complication was mainly related to luteal insufficiency and multiple pregnancies, whereas hyperstimulation was the major risk factor for bleeding in pregnancies arising from HMG-induced ovulation. Other currently unknown, aetiological factors for first trimester bleeding in IVF pregnancies remain to be investigated.

17 alpha-Hydroxyprogesterone Caproate

Induction of ovulation with D-Trp6-LHRH combined with purified FSH in patients with polycystic ovarian disease.

Seventeen patients with polycystic ovarian disease (PCOD) and evidence of mild or severe ovarian hyperstimulation syndrome (OHSS) during therapy with CC/hCG, FSH/hCG or hMG/hCG were treated with D-Trp6-LHRH until medical gonadectomy was attained. Under the suppressive therapy with the GnRH agonist (GnRHa) ovulation was induced with FSH/hCG. In 15 out of 17 patients, ovulatory cycles were obtained with this new modality of treatment. Seven patients conceived (3 viable pregnancies and 4 early abortions) after the 1st treatment cycle. Fourteen of the 17 patients demonstrated symptoms of mild OHSS which did not require hospitalization. Only 1 patient developed severe OHSS after the combined treatment. Our results suggest that therapy with GnRHa, especially in its delayed release formulation, is effective for the prevention of severe ovarian hyperstimulation in PCOD patients undergoing treatment with menotropins for the induction of ovulation.

Adult

Characterization of prolactin receptors and their distribution among American and Israeli women with breast cancer: implications for prediction of hormonal dependency and treatment.

A micro-method is reported for the determination and characterization of prolactin (PRL) receptors in human breast cancer specimens using either intact biopsy tissue or the pellet fraction remaining from biopsies previously processed for steroid hormone receptors. Labeled human PRL is used as the ligand. The specific PRL-binding of 307 human breast cancer specimens was evaluated by this micro-method. A significant level of specific PRL-binding (3-25 fmol per mg membrane protein) was detected in 41% of US breast cancer patients and 42% of Israeli patients. Scatchard analyses, performed on pooled membrane fractions with the highest specific PRL-binding revealed one class of receptors having a dissociation constant, Kd = 4.1 x 10(-9), and specific binding capacity, Bmax = 1.3 pmol per mg protein. These preparations were exposed to 3 M MgCl2, which dissociates the endogenous-bound PRL from the hormone-receptor complex and allows the characterization of the "total" PRL receptors. Two classes of receptors were then revealed. One class of receptors showed high affinity (Kd1 = 8.1 x 10(-10) M) and low capacity (Bmax1 = 335 fmol per mg protein), while the other possessed lower affinity (Kd2 = 8.2 x 10(-8) M), but a higher capacity (Bmax2 = 34.4 pmol per mg protein). Since PRL facilitates the growth of human breast cancer cell lines, these results indicate that a high proportion of human breast cancers may be PRL dependent. Routine determination of PRL receptors in biopsies of human breast cancer may permit the selection of a better treatment, since it is possible that the reduction in PRL levels could inhibit those tumors which are prolactin dependent.

Breast Neoplasms

Lack of relationship between the levels of prolactin receptors and steroid receptors in women with breast cancer.

The levels of prolactin receptors (PRL-R), based on a new micro-method, estrogen receptors (ER) and progesterone receptors (PG-R), were determined in 159 breast cancer specimens. Sixty-seven of 159 tumors (42%) had PRL-R levels of 20 fmol/mg protein or higher, and were regarded as PRL-R positive. In 60 of the 159 samples (38%), no PRL-R could be detected, and the remaining 32 samples (20%) were considered borderline. While a positive correlation was found between the presence of ER and PGR, no correlation was detected between PRL-R and any steroid receptors (r = -0.024 for ER vs PRL-R, 0.052 for PGR vs PRL-R and 0.002 for ER + PGR vs PRL-R). Furthermore, PRL-R in levels of 20 fmol/mg protein or higher were found in 35% of samples in which no steroid receptors were detected as well as in 38% and in 27% of samples which exhibited positive ER or PGR respectively (greater than or equal to 20 fmol/mg protein). On the other hand, in 47% of the samples possessing both ER and PGR, the PRL receptors could not be found. These results clearly demonstrate that in the human breast cancer, the presence of PRL-R is independent of the status of either ER or PGR. It is suggested that the measurement of PRL-R could serve as a chemical marker to guide a possible therapeutic use of PRL-suppressing drugs in women with breast cancer.

Adult

Micromethod for the determination of free and total prolactin receptors: measurement of receptor levels in normal and malignant mammary and prostate tissues.

A sensitive micromethod for the determination of free and total prolactin receptors in normal or malignant tissues has been developed. Positive and negative quality controls are incorporated in the procedure. Either whole tissue or the pellet fraction remaining from tissue that had undergone processing for estrogen receptors can be used. Crude microsomal and plasma membrane fractions obtained by homogenization and differential centrifugation are incubated with labeled prolactin in the presence or absence of increasing amounts of unlabeled hormone. The labeled ligand is prepared by a stoichiometric iodination procedure in which one atom of iodine-125 is incorporated into one molecule of the hormone, resulting in an intact labeled prolactin with a high specific activity of 170-186 muCi/micrograms (1 Ci = 37 GBq). Human prolactin labeled by this procedure has much greater specific binding capacity to various rat tissues than does iodinated rat prolactin. This technique permits an accurate measurement of prolactin receptors in as little as 50 micrograms of membrane protein. Highest levels of free and total prolactin receptors were found in the liver of 60-day-old female rats that served as a positive control. Liver of immature 21-day-old male rats, devoid of prolactin receptors, was used as a negative control. The amount of detectable free receptors was dependent on the level of circulating plasma prolactin. In 3-day postpartum lactating rats with high prolactin levels in plasma, all prolactin receptors in the mammary glands were found to be occupied, and no free receptors could be detected. When these receptors were desaturated from the endogenous prolactin by exposure to 3 M MgCl2, one class of receptors in a high quantity (1.75 nmol/mg of protein) and with a moderate affinity (Kd = 6.41 X 10(-9) M) was detected. A similar type of receptor was found in the mammary glands of rats at midpregnancy and of cycling adult female rats. In malignant rat mammary tissue, however, fewer receptors (27 pmol/mg of protein) but with a very high affinity (Kd = 6.8 X 10(-14) M) were detected. Normal ventral and dorsolateral rat prostate contained two classes of prolactin receptors (Kd = 3.46 X 10(-10) M and 1.93 X 10(-8) M). In the cancerous rat prostate, however, only one of these two classes of receptors was detected, and the number was smaller.

Animals

Hematoma of the umbilical cord with acute antepartum fetal distress. A case report.

In a case of spontaneous hematoma of the umbilical cord, no pathologic lesion was found in the umbilical blood vessels. However, an extremely short cord (14 cm) may have contributed to the vessel rupture. A prolonged deceleration discovered during a routine nonstress test led to emergency cesarean section, with delivery of a healthy neonate.

Cesarean Section

Sulpiride-induced hyperprolactinemia and impotence in male psychiatric outpatients.

The relationship between erectile dysfunction and sulpiride stimulatory effect on prolactin secretion was studied in 13 married male psychiatric outpatients. The patients population was comprised of 2 groups: patients with anxiety disorders resistant to minor tranquilizers who were treated with sulpiride up to 200 mg/day, and schizophrenic patients treated with sulpiride 600 mg/day. All the patients were maintained on maximal dose for a period of 3 weeks. Sexual function and blood prolactin levels were monitored once weekly. The patients who developed impotence were maintained on higher doses of sulpiride and exhibited higher prolactin levels in comparison to the potent patients. Restoration of potency was observed after reduction or discontinuation of sulpiride treatment. It is concluded that sulpiride induced impotence is associated with hyperprolactinemia.

Adult

Prolactin response to the cold pressor test in patients with panic attacks.

Recent advances in psychiatric nosology have provided a clearer clinical description of panic disorder and agoraphobia with panic attacks. This clinical improvement has yet to result in a better understanding of the basic mechanisms involved in these conditions. The present study compares the effects of the cold pressor test on blood pressure changes and prolactin levels in patients with panic disorder and agoraphobia with panic attacks to its effects in normal controls. Because the effects of the cold pressor test were similar in patients and normal controls, it appears that alpha-adrenergic function is normal in the patient group. The results also suggest that prolactin hypersecretion does not occur in pathological anxiety states.

Adult

Transient hyperprolactinemia: a correctable cause of idiopathic female infertility.

Frequent measurements of prolactin throughout the menstrual cycle were obtained in 48 women with regular menses and longstanding idiopathic infertility. Forty-five of the 48 patients (94%) had a small but significant transitory preovulatory elevation in their serum prolactin levels (hPRL). These transitory elevations in hPRL to 27-70 ng/ml lasted only one to three days and coincided with the preovulatory estradiol peak. When this transient hyperprolactinemia was suppressed by treatment with an appropriate, titrated dose of bromergocriptine, 18 patients (40%) conceived within one to three months. Evidently, this transitory, relatively mild hyperprolactinemia was not sufficient to interfere with follicular maturation, ovulation, or corpus luteum function, but it may impair fertilization and/or implantation.

Adult

Maternal and fetal serum prolactin levels in cases of premature rupture of membranes.

Serum prolactin levels were measured in maternal and fetal sera immediately post delivery in 20 cases of premature rupture of the membranes and in 20 controls. Fetal serum prolactin levels were 781 +/- 265 ng/ml in cases of PRM and 737 +/- 314 ng/ml in controls. Maternal serum prolactin levels were 504 +/- 264 ng/ml in cases of PRM and 731 +/- 361 ng/ml in controls. This difference is statistically significant (t = 1.81, p less than 0.05). A probable role of prolactin in maintaining fetal membrane integrity and the probable effect of the difference in maternal serum prolactin concentration in the two groups on the membranes' viscoelastic properties is discussed.

Elasticity

Human ovarian receptors to human prolactin: implications in infertility.

In the human, hyperprolactinemia may interfere with fertility. To find out whether or not prolactin (PRL) can act directly on human ovarian tissues, in vitro studies involving specific binding of human PRL to various human ovarian elements were carried out. Human PRL was isolated from amniotic fluid, and its intact monomeric iodinated isohormone B was prepared. Labeled PRL was incubated with plasma membranes of either granulosa or whole follicular homogenates. Relatively high specific binding sites were obtained. Saturation studies and Scatchard analysis showed a single class of binding sites with high binding affinity (Kd = 1.8 x 10(8) M) and a concentration of 7.9 x 10(-15) moles/mg protein. These results clearly demonstrate the existence of specific receptors to isoprolactin B in ovarian elements with binding capacity and concentration at least equal to that found in other targets for PRL. It is reasonable to assume that hyperactivation of these receptors in states of hyperprolactinemia constitutes the cause for the disturbances in ovarian functions that lead to infertility.

Binding, Competitive

Oxytocin-stressed and unstressed cardiotocograms for the prediction of fetal compromise.

The results of unstressed and oxytocin-stressed cardiotocograms recorded in 222 high-risk pregnancies within 48 h of delivery were compared with signs of fetal distress in labour and Apgar scores. Thirty-nine (18%) developed a late deceleration pattern in labour and 18 newborn (8%) had Apgar scores of less than 7 at 1 min. A direct comparison of the predictive value of unstressed and stressed cardiotocograms, using Fisher's exact test, showed a very significant difference in favour of the stressed cardiotocogram for the prediction of both fetal compromise and fetal well-being. The exclusion, or very selective use, of the oxytocin-stressed cardiotocogram and reliance on the unstressed cardiotocogram for the antepartum investigation of high-risk pregnancies sacrifices accuracy for convenience.

Adolescent

Conservative management of suspected prolactin secreting pituitary adenoma during pregnancy.

Seventeen women with prolactin levels of 100 ng/ml and above suspected of harboring prolactin-secreting pituitary adenoma, from the basis of this study. Ten patients had radiological signs of an adenoma while in 7 the radiological criteria for such a diagnosis were not fulfilled. Ovulation and pregnancy were induced with bromocriptine in all 17 patients. They were carefully observed during pregnancy and following delivery. All gave birth to full-term babies after uneventful pregnancies, except for one patient who experienced intrauterine fetal death at 31 wk of gestation. It is our policy that women with suspected intrasellar prolactin-secreting pituitary adenoma be allowed to conceive and give birth without previous surgical intervention. The patient should be closely followed during pregnancy for clinical symptoms of enlargement of the tumor, including periodic visual field examinations. In cases of neurologic or ophthalmologic complications, surgery or bromocriptine administration without interruption of pregnancy is advocated, or if lung maturity is achieved, delivery should be induced.

Adenoma

Prolactin concentration in prostates with benign hypertrophy.

Twenty-two hypertrophied prostates removed in surgery were checked for prolactin concentration by the radioimmunoassay method. The mean concentration in the prostatic tissue was found to be 38.2 +/- 1.9 ng./Gm. while the mean basal serum level was 11.9 +/- 1.3 ng./ml. It is concluded that serum prolactin levels do not reflect prostatic prolactin concentration. The possibility that interrelationship in action exists between androgens and prolactin affecting each other's concentration, both influencing prostatic metabolism is discussed.

Aged