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Biomedical subjects

B B Bercu

Publications and source records attributed to B B Bercu.

At least 73 records · Page 4Linked to original sources
PubMed1983

Sertoli cell maturation is impaired by neonatal passive immunization with antiserum to luteinizing hormone-releasing hormone.

Male rats treated with a single injection of antiserum to LHRH (LHRH-AS) at 5 days of age have small testes as adults. In the present investigation, the serial maturation of the hypothalamic-pituitary-gonadal axis was studied in young male rats passively immunized with LHRH-AS. Testicular and epididymal weights, serum androgen and gonadotropin levels, testicular receptors for human CG (hCG), and androgen binding protein (ABP) concentrations in serum, testis, and epididymis were compared in developing animals treated with a single ip injection of LHRH-AS or normal rabbit serum. Rats treated with LHRH-AS had lower serum concentrations of ABP at all ages; the highest levels were on days 22-24, which were several days later than controls. Testicular weight was about 60% that of the control at all ages from 10-90 days. A reduction in epididymal weight to 80% that of the control was seen only in adults at days 60 and 90. Testicular ABP content increased steadily with age, but its concentration peaked at day 17 for controls and day 22 for LHRH-AS treated animals. Both testicular and epididymal ABP content were commensurate with testicular weight in controls and treated rats through day 45. Similarly, hCG-receptor content and concentration increased steadily with age, but differences between control and treated groups paralleled testicular weight. These results suggest an effect of LHRH blockade at a critical period which impairs early testicular growth and causes a permanent reduction in growth. Sertoli cell function and hCG-receptor appearance are impaired in proportion to this reduction.

Aging↗
PubMed1983

Effect of GnRH antagonist, [Ac-delta 3Pro1, pFDPhe2, DTrp3,6] GnRH, on pulsatile gonadotrop in secretion in the castrate male primate.

Three different doses of a potent antagonist to GnRH, [Ac-delta 3Pro1, pFDPhe2, DTrp3,6], GnRH were compared in adult male monkeys to determine the acute effect on pulsatile gonadotropin secretion. In accomplishing these studies, blood was drawn at 15 min intervals over 24-30 h without anesthesia using a mobile vest and tether assembly to support an indwelling cannula. After a 3 to 6 h control period, 2.0, 0.2 or 0.02 mg GnRH antagonist/kg bw in 1 ml corn oil sc, was given to castrate adult monkeys. The highest dose decreased circulating LH (by radioimmunoassay and bioassay) and FSH whereas the intermediate dose decreased LH only. The higher dose produced both a more prolonged and greater reduction in circulating gonadotropins. These data demonstrate that this GnRH antagonist can reduce serum gonadotropins both acutely and for intervals greater than 24 h.

Animals↗
PubMed1983

Male sexual development in the monkey. I. Cross-sectional analysis of pulsatile hypothalamic-pituitary-testicular function.

Pulsatile secretion of serum gonadotropins and testosterone was studied in 46 monkeys of varying ages from 9 days of age through adult life. Although some of the hormonal analysis was longitudinal in nature, most comparisons were cross-sectional. On the basis of pulsatile secretory patterns, hCG and GnRH stimulation, skeletal age, testicular volume, and histology, we have arbitrarily defined four developmental age groups: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In accomplishing the pulsatile studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling cannula. GnRH and hCG challenge tests were done on one or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH, LH, testosterone, dihydrotestosterone and delta 4-androstenedione by established RIAs and an in vitro bioassay for LH. During the frequent sampling period of 24-h duration for all except postnatal animals, testosterone pulses of large amplitude (up to 8-fold) occurred in postnatal, pubertal, and adult animals. Pulsatile gonadotropin secretion was seen at all ages; however, the highest pulses (up to 15-fold) occurred in prepubertal animals even though this was an infrequent occurrence. Time series analysis techniques were applied for objective statistical characterization of cyclic patterns. Basic rhythms corresponding to 50- to 90-min frequency cycles in gonadotropin secretion were identified. Substantive differences between LH concentrations by bioassay and RIA were seen infrequently. Our findings illustrate that: 1) circulating gonadotropin and testosterone pulses change in amplitude but not necessarily frequency during pubertal development, and 2) primate models are a useful paradym for the longitudinal study of human male sexual development. We conclude that where direct human investigation may be limited, much can be learned by study of these primate surrogates.

Age Determination by Skeleton↗
PubMed1983

Male sexual development in the monkey. II. Cross-sectional analysis of pulsatile hypothalamic-pituitary secretion in castrated males.

Pulsatile secretion of serum gonadotropins was studied in 16 castrated monkeys from 4 weeks of age through adult life. Animals were castrated at various ages from birth through adult life. Although some studies of the gonadotropin-secretory patterns were longitudinal in nature, most comparisons were cross-sectional. On the basis of our observations, we have arbitrarily grouped the animals into 4 developmental ages: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In carrying out these studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling catheter. GnRH challenge tests were done on 1 or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH and LH by established RIAs and an in vitro bioassay for LH. During the frequent sampling period (24 h for all except postnatal animals), the amplitude of gonadotropin pulses was greatest in adult animals followed by postnatal and pubertal monkeys. During pubertal development, there was a marked increase in the magnitude of gonadotropin pulses, and remarkedly, there was a substantial increase in the LH bioassay: RIA (greater than 5:1) by adult life. GnRH challenge tests of gonadotropins correlated with these observations. Time series analysis was applied to the data for objective statistical characterization of cyclic patterns. Our findings can be summarized: 1) during pubertal maturation there is a change in amplitude but not frequency of gonadotropin pulses, 2) pubertal development of the hypothalamic-pituitary axis advances in the absence of gonadal feedback, and 3) there is a significant increase in the LH bioassay: RIA during pubertal development. We conclude that the castrate monkey is a valuable adjunct to direct clinical investigations of the mechanisms controlling human sexual development.

Age Factors↗
PubMed1982

Neutralization of gonadotropin-releasing hormone in neonatal rats with permanent impairment of the hypothalamic-pituitary-testicular axis.

Males rats were passively immunized at 5 days of age with a single 0.25 ml i.p. injection of gonadotropin-releasing hormone (GnRH) antiserum. Control animals were given an equal volume of normal rabbit serum (NRS). Serial blood determinations of gonadotropins, testosterone and dihydrotestosterone (DHT) were obtained at intervals ranging from early in life through adult life. Gonadotropin secretion was reduced (P less than 0.025) up to 35 days of age. Androgen secretion (testosterone) was reduced (P less than 0.05) at 10 and 33 days of age. When hCG was given to 54-day-old (young adult), and 100-day-old and 15-month-old animals, testosterone concentrations were similar in both experimental and control groups 1 h after hCG stimulation. As adults, basal gonadotropins were the same in both groups; however, after GnRH stimulation, the GnRH antiserum-treated groups showed an increased gonadotropin response when compared to the NRS control group. In order to determine whether there was an alteration in steroid feedback, other animals were castrated at adult age (approximately 100 days old), and exogenous testosterone was given in increasing increments. However, serum gonadotropins decreased similarly in treated and control groups. These data indicate that a single injection of GnRH antiserum early in life decreased gonadotropin secretion temporarily during prepubertal sexual development and caused a permanent alteration in hypothalamic-pituitary-testicular function.

Animals↗
PubMed1982

Pharmacologic effects of melatonin on hypothalamic-adenohypophyseal function in the nonhuman primate.

The pharmacologic effects of intravenous melatonin on hypothalamic-adenohypophyseal function were studied in male rhesus monkeys (n = 10) and compared to control animals (n = 9-13). Basal and arginine- or L-dopa-stimulated values of growth hormone in melatonin-treated animals were similar to those of control primates. Insulin-stimulated growth hormone secretion was slightly decreased. Melatonin did not affect basal or thyroid stimulating hormone releasing hormone (TRH)-stimulated values of thyroid stimulating hormone (TSH) or prolactin. No effects were seen on basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) or follicle stimulating hormone (FSH) secretion.

Animals↗
PubMed1982

Effects of cranial radiation on hypothalamic-adenohypophyseal function: abnormal growth hormone secretory dynamics.

The function of the hypothalamic-adenohypophyseal unit was tested in 2 groups of rhesus monkeys before and at periodic intervals after the administration of 2400 and 4000 rads cranial radiation. This therapy was given in 10 fractions over a 2-week period. Plasma TSH, basally and after TRH administration, and LH and FSH, before and after gonadotropin-releasing hormone stimulation, were normal up to 1 yr after radiation. Plasma GH at the basal state and after arginine and L-dopa stimulation was also normal. An insulin tolerance test, however, demonstrated a blunted GH response at a dose (0.1 U/kg) that caused brisk stimulation of GH secretion in normal control monkeys. A larger dose of insulin (0.2 U/kg) resulted in ample secretion of GH in these animals, suggesting decreased hypothalamic sensitivity to insulin in treated animals. The measurement of GH every 20 min for 24 h in animals treated with 4000 rads showed a dramatically altered secretory pattern of GH 1 yr after radiation. GH secretory spikes were markedly decreased in both frequency and amplitude, suggesting a reduction in the normal daily production of GH.

Animals↗
PubMed1981

Hypothalamic-adenohypophyseal function in male rhesus monkeys. A primate model.

The secretion of six anterior pituitary hormones in both the basal state and after stimulation or suppression in nine young adults male rhesus monkeys (Macaca mulatta) was studied. Growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) secretion were evaluated. Adrenocorticotropin hormone (ACTH) secretion was studied indirectly by measuring plasma cortisol levels. The tests were performed in combination and in sequence over a 7-hour period. Thus, multiple functions of the hypothalamic-hypophyseal axis can be studied quickly utilizing small quantities of blood.

Animals↗
PubMed1980

Pituitary resistance to thyroid hormone in cystinosis.

Eleven children with nephropathic cystinosis without clinical features of hyperthyroidism or hypothyroidism had elevated serum levels of immunoreactive TSH. The mean TSH level (+/- SE) was 37.4 +/- 12.3 microM/ml. Serial determinations of thyroid function during 1 yr were: mean (+/- SE) serum T4, 10.8 +/- 0.7 microgram/dl; free T4, 2.1 +/- 0.2 ng/dl; and T3, 239 +/- 6 ng/dl. After 500 microgram TRH iv, the peak TSH level exceeded 100 microU/ml in 6 of 10 patients, whereas T3 responses were variable. Studies of parameters influenced by thyroid hormone, including red cell sodium content, serum cholesterol, and 24-h urinary hydroxylysine excretion, were consistent with euthyroidism. On the other hand, the mean pulse wave arrival time was significantly reduced, consistent with hyperthyroidism. Three control patients, 2 with Lowe's syndrome and 1 with benign cystinosis, had normal thyroid studies. Eight of the patients were given either exogenous L-T4 or T3 in doses which were increased at weekly intervals. The serum TSH concentrations were suppressed to normal only after elevation of serum levels of thyroid hormones and with high exogenous thyroid replacement doses. The data suggest abnormal pituitary resistance to feedback by thyroid hormone in patients with cystinosis. We believe this to be the first description of the association of a heritable metabolic disease with such pituitary resistance.

Child↗
PubMed1980

Response of adult male rats to LH-RH after neonatal immunization with antiserum to LH-RH.

Male rats were passively immunized at Day 5 of age with LH-RH antiserum. Their response to LH-RH at 100 days of age was examined. Serum FSH and LH concentrations increased more than in control rats, although basal plasma levels were similar. The pituitary content of LH, but not FSH, was significantly increased, and hypothalamic content of LH-RH was similar in both groups. The testes and seminal vesicles were smaller in experimental animals than in controls. It is suggested that transient blockade of LH-RH secretion during the neonatal period produces abnormalities in pituitary-testicular functon in the adult rat.

Animals↗
PubMed1979

Hypothalamic-pituitary dysfunction following CNS prophylaxis in acute lymphocytic leukemia: correlation with CT scan abnormalities.

In an attempt to identify possible adverse effects of CNS prophylaxis (cranial radiation and intrathecal chemotherapy), we examined hypothalamic-pituitary function in 23 patients with acute lymphocytic leukemia (ALL). Of 18 patients who had received both cranial radiation and intrathecal chemotherapy, nine had abnormally low growth hormone responses to insulin-induced hypoglycemia (less than 7.0 ng/ml). Seven of the nine patients with abnormally low growth hormone responses also manifested ventricular dilatation on computed tomography (CT) brain scans, whereas only one of the nine patients with normal growth hormone responses demonstrated this CT scan finding (P = 0.015). The remaining patients, who had not received cranial radiation, had normal growth hormone responses and normal CT scans. There is significant correlation between ventricular dilatation on CT and abnormally low peak growth hormone responses following CNS prophylaxis in ALL.

Adolescent↗
PubMed1979

The pulse wave arrival time (QKd interval) in normal children.

The interval between the onset of QRS of the electrocardiogram and the arrival of the pulse wave at the brachial artery, as detected by the appearance of Korotkoff sounds at diastolic pressure (QKd), provides a measure of a pulse wave arrival time, i.e., the sum of the pre-ejection period and a pulse transmission time. This measurement has proven useful in the evaluation of cardiovascular disease, thyroid and catecholamine status, and several other conditions in adults. In order to standardize this measurement in children, measurements were obtained on 63 normal children ranging in age from 7 months to 18 years. Because of the dependence of pulse transmission time on the distance of propagation, the QKd interval (in msec) is related to height (H in cm) by the equation: QKd = 56.6 + 0.797H. By use of this equation one can obtain a "height corrected QKd." Correction for pulse rate is not necessary for resting subjects. These normal ranges permit use of the QKd interval for clinical studies in children. These studies also permit measurement of the mean pulse wave velocity for a group of individuals. PWV (m/sec) increases with age according to the equation: PWV = 2.44 + 0.203 A, (A in years) with a correlation coefficient of r = 0.823. This implies progressive loss of functional elasticity of the major arteries throughout childhood.

Adolescent↗