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Biomedical subjects

I Z Beitins

Publications and source records attributed to I Z Beitins.

At least 73 records · Page 4Linked to original sources

Phenotypic delineation of ring chromosome 15 and Russell-Silver syndromes.

A male child with features of the Russell-Silver syndrome, including pre- and postnatal growth delay, triangular facies, bilateral fifth finger clinodactyly, and disproportionate lower extremities, was found to have a ring chromosome 15 in all peripheral leucocytes examined. Review of the reported cases of ring chromosome 15 defines a malformation syndrome with a characteristic facies related to deletion of the 15q26.2----qter region. Russell-Silver and ring 15 syndromes share clinical features such as growth deficiency, triangular facies, digital anomalies, and café-au-lait spots. Microcephaly, mental retardation, facial dysmorphology, limb anomalies, and cardiac defects are more striking in ring chromosome 15 patients and are indications for karyotyping when found in conjunction with the Russell-Silver phenotype.

Chromosome Aberrations↗

Effect of carbohydrate supplementation on reproductive hormones during fasting in men.

We previously demonstrated that during a 10-day fast in mildly obese men, urinary gonadotropin excretion significantly increased, and serum testosterone concentrations significantly decreased. The mechanisms by which these changes occur are unknown. We postulated that the mechanism of the gonadotropinuria might involve decreased proximal renal tubular reabsorption of gonadotropins during fasting and might be related to renal tubular reabsorption of ketones during fasting, a process that is enhanced by carbohydrate (CHO) administration. We studied the effects of CHO supplementation on ketosis, ketonuria, and reproductive hormone secretion and excretion in 14 mildly obese men, 24-54 yr old, who were 14-69% above ideal body weight. Group I (n = 6) received no CHO supplementation, group II (n = 4) received 15 g CHO, and group III (n = 4) received 45 g CHO daily during the 10-day fast (F). During the control (C) and refeeding (R) periods, all subjects received a 1500-cal diet. Daily 24-h urine collections were made for the measurement of total ketones (millimolar concentrations) and LH and FSH (expressed as international units of the Second International Reference Preparation of human menopausal gonadotropin). Values (mean +/- SE) for 3 representative days (control day 3, fasting day 8, and refeeding day 3) for all subjects are shown below: (table; see text) We also studied the effects of CHO supplementation on serum levels of pituitary gonadotropins, LH and FSH responses to exogenous LHRH stimulation, biological activity of LH, and circulating total and free testosterone levels. Neither dose of CHO prevented the decline in total and free testosterone levels. Serum LH concentrations, as measured by both the RIA and in vitro bioassay did not change significantly with fasting. Serum FSH concentrations in daily samples did not change significantly. The previously reported decline in the FSH response to LHRH stimulation with fasting was not prevented by CHO. We conclude that CHO supplementation prevents the gonadotropinuria of fasting in men. The effect appears to occur in the kidney. The mechanisms may be related to that by which CHO promotes the renal tubular reabsorption of ketones. The reduced serum testosterone level cannot be explained by a lack of biologically active LH. It appears that fasting has a direct effect on the testis, possibly by reducing its responsiveness to gonadotropic stimulation or by inhibiting steroidogenesis.

Adult↗

Hormonal responses to short term fasting in postmenopausal women.

Urinary excretion of gonadotropins increases during fasting. We investigated whether this increase results from increased pituitary secretion of LH and FSH or from altered renal excretion of protein molecules. To this end, we studied urinary gonadotropin excretion, serum gonadotropin levels, and pituitary responsiveness of LHRH during control, 10-day fasting, and refeeding periods in 10 mildly obese postmenopausal women. Additionally, we measured urinary cortisol and estriol excretion and circulating levels of dehydroepiandrosterone sulfate, estradiol, estrone, melatonin, norepinephrine, epinephrine, and dopamine during the control, fasting, and refeeding periods. While urinary excretion of gonadotropins increased markedly during fasting, there were no significant changes in serum gonadotropin levels or in the pituitary sensitivity to LHRH. Plasma norepinephrine and serum melatonin increased significantly during fasting, but serum and urinary estrogens, indices of adrenal activity, and plasma levels of epinephrine and dopamine did not change. These results show that the stress of short term fasting selectively activates only certain components of the neuroendocrine system without any appreciable changes in the function of the gonadotropin-secreting system. Fasting-induced gonadotropinuria is probably explained by altered renal handling of gonadotropin molecules.

Adult↗

Endurance training effects on plasma hormonal responsiveness and sex hormone excretion.

A prospective study of the hormonal effects of a moderate exercise training program (4-wk control, 8-wk training) was conducted in seven young women. Sixty-minutes continuous bicycle ergometer tests of fixed relative intensity were performed at the beginning, middle, and end of the training period. The capacity of these acute bouts of exercise to affect circulating levels of stress markers, reproductive hormones, and hormones with possible antireproductive potential was measured. In addition, the urinary excretion of reproductive hormones was monitored continuously via serial overnight urine collections. Within testing sessions, plasma concentrations of all stress markers and antireproductive hormones rose significantly. Across testing sessions, only beta-endorphin + beta-lipotropin and cortisol exhibited an increment in peak responses as training progressed. Plasma reproductive hormone levels showed insignificant acute changes, and cyclic menstruation and preovulatory gonadotropin surges continued in all subjects. However, ovarian function was disturbed in four subjects as evidenced by a decreased excretion of estriol, free progesterone, or both. Transient infertility is a known clinical accompaniment of hormonal changes of comparable subtlety.

Adolescent↗

Biologically active luteinizing hormone is secreted in episodic pulsations that vary in relation to stage of the menstrual cycle.

To characterize the physiological pattern(s) of bioactive LH secretion in normal women, serial blood samples were withdrawn at frequent intervals in each of six women at three different stages of the menstrual cycle. Plasma LH concentrations were quantitated in each sample by both rat interstitial cell testosterone ( RICT ) bioassay and immunoassay (RIA). When the resulting RICT and RIA LH profiles were systematically compared, we found that mean (and integrated) plasma concentrations of bioactive LH were approximately 2-fold higher than immunoactive LH levels at all stages of the menstrual cycle. In addition, unequivocal prominent pulsations of bioactive LH could be demonstrated in these women throughout the normal menstrual cycle. For all stages of the menstrual cycle, bioactive to immunoactive LH ratios within LH pulses were significantly (P less than 0.01) increased over these ratios in the interpulse periods. The frequency of bioactive LH pulses increased dramatically from 0.44 +/- 0.24 (+/- SD) pulses/h in the early follicular phase to 1.21 +/- 0.07 pulses/h in the late follicular phase (P less than 0.003), and then declined to only 0.25 pulses/h in the luteal phase (P less than 0.001). Notably, significant discordance existed between bioactive and immunoactive LH pulses, with 30% of immunoactive and 14% of bioactive LH pulses occurring alone. In conclusion, using the RICT , we demonstrated that biologically active LH is secreted in discrete episodic pulsations in normal women. Estimates of the bioactive to immunoactive LH ratio indicate that these pulses of LH are preferentially enriched in biologically active compared to immunoactive hormone. The properties of bioactive LH pulses are under physiological control, since the amplitude and frequency of bioactive LH pulses vary significantly in relation to phases of the menstrual cycle. Since significant discordance exists between immunoactive and bioactive LH pulsations in normal women, we suggest that estimates of the circulating concentrations of biologically active LH (rather than immunoactive LH alone) are necessary to characterize fully physiological patterns of LH secretion during the menstrual cycle.

Adult↗

Gonadotropin and prolactin pulsations in hyperprolactinemic women before and during bromocriptine therapy.

Pulsatile gonadotropin secretion and its relationship to PRL and estradiol (E2) secretion were investigated in 20 hyperprolactinemic amenorrheic women by obtaining serial blood samples for 6- to 24-h periods. Thirteen patients were restudied in the early follicular phase of the menstrual cycle (days 3-5) after ovulatory periods were established during bromocriptine therapy. In the hyperprolactinemic women, the number of LH peaks ranged from 0-12/24 h, and LH peak amplitude ranged from 0-1.7 mIU/ml. Serum E2 correlated with mean LH concentrations (P less than 0.001) and LH pulse frequency (P less than 0.05), but not with LH pulse amplitude. FSH pulsations were identified in 3 of the 20 women. There was no correlation between mean FSH concentrations and either serum E2 or PRL. There was a significant correlation between LH and FSH concentrations (P less than 0.001). During bromocriptine therapy, with comparable E2 concentrations, 5 of the 6 patients studied with blood sampling every 20 min for 24 h had a significant decrease (P less than 0.01) in the number of LH peaks per 24 h, with no change in LH peak amplitude. Mean FSH concentrations were unchanged in bromocriptine-treated patients; however, there was a significant (P less than 0.02) decrease in FSH levels during sleep. Serum PRL was normal in all bromocriptine-treated patients, but normal PRL secretory patterns were not reestablished, and there was no correlation between LH pulsations and serum PRL concentrations. We conclude that 1) hyperprolactinemic women have a heterogeneous pattern of pulsatile gonadotropin secretion; 2) serum E2 correlates with LH pulse frequency but not pulse amplitude; 3) LH pulsations and PRL pulsations are asynchronous in hyperprolactinemic women before and during bromocriptine therapy; and 4) normal PRL secretory patterns are not required for ovulatory function in hyperprolactinemic women treated with bromocriptine.

Adenoma↗

alpha-Subunit and gonadotropin responses to luteinizing hormone-releasing hormone in hyperprolactinemic women before and after bromocriptine.

alpha-Subunit and gonadotropin responses to a LHRH infusion (0.2 micrograms/min) for 4 h were studied in eight hyperprolactinemic amenorrheic women, ages 23-40, and in five normal women in the early follicular phase of the menstrual cycle. Basal alpha-subunit and LH concentrations were comparable to normal women; however, basal FSH concentrations were significantly (P less than 0.05) lower. Peak serum alpha, LH, and FSH concentrations during the LHRH infusion were significantly higher than controls (P less than 0.01, P less than 0.05, and P less than 0.01, respectively). Gel chromatography of serum confirmed the presence of both free alpha-subunit and intact LH which had normal biological activity. Six of the women were restudied in the early follicular phase of the cycle after return of normal ovulatory function and normalization of serum PRL concentrations. During bromocriptine therapy, peak serum alpha, LH, and FSH concentrations decreased significantly (P less than 0.02, P less than 0.05, and P less than 0.001, respectively) and were comparable to control subjects. The changes in serum alpha and gonadotropin responses to the LHRH infusion during bromocriptine therapy occurred independently of the serum estradiol concentrations. Abnormalities in the regulation of alpha-subunit and gonadotropin secretion are present in hyperprolactinemia. These abnormalities reverse with bromocriptine therapy and may occur independently of changes in gonadal steroids.

Adult↗

Mode of secretion of bioactive luteinizing hormone in man.

The episodic nature of gonadotropin secretion was originally defined by RIA of circulating LH concentrations. We analyzed the pulsatile release of biologically active LH by measuring plasma LH concentrations in the rat interstitial cell testosterone bioassay. A computer algorithm to discriminate true biological signals (LH pulses) from background variation was applied to serially sampled LH data from seven men and seven postmenopausal women. Our results indicate the following. 1) In all subjects, mean bioactive LH values were considerably higher than immunoactive levels, (41.4 +/- 15.1 and 450 +/- 243 mIU/ml vs. 10.2 +/- 2.3 and 83 +/- 35 for men and postmenopausal women, respectively). There was a corresponding 4-fold increase in the total area under the bioactive LH secretion profile compared with that defined for the immunoactive hormone. 2) The absolute amplitude of the bioactive LH peaks was 0.5- to 11-fold higher than the immunoactive values. 3) Although the majority of the LH peaks were coincident by bioassay and RIA, significant dissociation occurred in 20% and 28% of the total LH peaks (rat interstitial cell testosterone bioassay and RIA) in men and postmenopausal women, respectively. 4) Significant increases in the bioactive to immunoactive ratio over interpulse bioactive to immunoactive levels occurred in 98% of the pulses in the men and 83% of those in postmenopausal women. Also, in two men, peaks of LH bioactivity exceeding 100 mIU were followed by major increases in serum testosterone concentrations. These findings demonstrate the value of bioactive LH determinations and indicate that LH is secreted in pulses of high biological activity. The in vitro LH bioassay provides a sensitive and appropriate estimate of functionally active LH in the circulation.

Adult↗

Pure alpha-secreting pituitary adenomas.

Isolated hypersecretion of the alpha subunit of the glycoprotein hormones occurred in two men with previously diagnosed "nonfunctioning chromophobe adenomas." The alpha hypersecretion was unresponsive to hypothalamic releasing hormone, thyroid hormone, and sex-steroid hormones. After trans-sphenoidal surgery and conventional pituitary irradiation, alpha secretion was decreased. Increased quantities of immunologically active and biologically inactive luteinizing hormone (LH) material were detected in serum and in tumor homogenate. Immunologic and gel-chromatographic studies determined that only the alpha subunit was present and that it was cross-reacting in the LH immunoassay. These studies suggest that the alpha subunit may be a useful marker of pituitary tumors, particularly in patients without clinical evidence of hormonal hypersecretion.

Adenoma, Chromophobe↗

Testicular leydig cell hyperplasia as a cause of familial sexual precocity.

Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.

Child, Preschool↗

Reproductive function during fasting in men.

To investigate reproductive function during fasting, six men 20-74% over ideal body weight completed an 18-day study consisting of a 3-day control period, a 10-day total fast, and a 5-day refeeding period. All men lost at least 4.1% of total weight and demonstrated ketonemia and ketonuria. The FSH response to LRH (0.2 microgram/min for 4 h) stimulation was significantly lower (P less than 0.05) during fasting and remained so during refeeding. Serum FSH concentrations were significantly lower (P less than 0.05) during the fast in five of six patients compared to those during the control period, whereas serum LH concentrations were unchanged. The effects of fasting on endogenous LH and FSH pulsations were studied by obtaining serum at 20-min intervals for 6 h on days 2, 11, and 16. Neither the amplitude nor the frequency of LH and FSH pulsations changed significantly during fasting or refeeding. Serum testosterone concentrations were significantly lower (P less than 0.025) by fasting day 9 compared to control values. The 24-h urinary excretion of both LH and FSH increased significantly (P less than 0.05) by fasting day 6 and reached a maximum by fasting day 8. Urinary LH excretion did not return to normal after 3 days of refeeding, whereas urinary FSH excretion returned to baseline by the first day of refeeding. We conclude that during short term fasting in obese men: 1) serum FSH concentrations decrease, 2) the pituitary responsiveness of FSH and LRH is blunted, 3) serum testosterone decreases, and 4) the urinary excretion of both LH and FSH increase.

Adult↗

Reduction of plasma immunoreactive somatomedin C during fasting in humans.

We have assessed the effect of fasting for 10 days on plasma concentrations of immunoreactive somatomedin C and urinary urea excretion in seven obese male volunteers. From a mean prefast value of 0.83 U/ml, plasma somatomedin C fell to 0.21 U/ml after 10 days of fasting. A prompt increase was observed with refeeding. The change in somatomedin C during fasting showed a highly significant correlation with the change in urinary urea nitrogen excretion (r = 0.74; P less than 0.001). It also was shown that inhibitors which interfere with quantitation in somatomedin bioassays are not observed in the RIA for somatomedin C. The results of this study suggest that measurement of plasma somatomedin C provides a sensitive indicator of nitrogen loss and may be useful in monitoring the changes in protein metabolism that occur during alterations in nutritional status.

Adult↗

Menstrual abnormalities during adolescence.

A thorough understanding of the events and hormonal changes which accompany puberty can be successfully utilized to diagnose adolescent menstrual disorders. Knowledge regarding the maturational events within the hypothalamic-pituitary-ovarian axis and the expected times at which positive feedback leading to ovulation occurs is helpful in the design of optimal therapeutic regimens. It should be emphasized that the immature hypothalamic-pituitary-ovarian axis is extremely sensitive to low doses of estrogen and suppression may hinder maturation to normal cyclic activity. Therefore, forms of therapy other than oral contraceptives should be sought and prescribed for adolescents with menstrual disorders.

Adolescent↗