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Biomedical subjects

I Z Beitins

Publications and source records attributed to I Z Beitins.

At least 91 records · Page 5Linked to original sources
PubMed1980

The biologic activity of a potent analogue of gonadotropin-releasing hormone in normal and hypogonadotropic men.

We studied the biologic activity of a long-acting analogue of luteinizing hormone-releasing hormone, D-Trp6-Pro9-NEt-LHRH (LHRHa), in five normal men and four hypogonadotropic men previously unresponsive to natural LHRH. All subjects responded to LHRAa, but there were quantitative and qualitative differences between the normal and hypogonadotropic men. Normal men showed a linear dose-response relation, endogenous gonadal steroid secretion, and an adult pattern of gonadotropin secretion characterized by a high ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH). Hypogonadotropic men had improving pituitary responses to each dose of LHRHa (priming response), no demonstrable gonadal steroid secretion, and a prepubertal pattern of gonadotropin release characterized by reversal of the normal ratio of LH to FSH. When compared with native LHRH, LHRHa had an augmented ability to discharge gonadotropins acutely and to sustain their release in normal and hypogonadotropic men.

Adolescent↗
PubMed1980

Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro.

The effects of LHRH and a potent LHRH agonist (LHRHa) on invitro testosterone production by enzyme-dispersed rat interstitial cells were evaluated. In a series of in vitro experiments, neither basal nor human menopausal gonadotropin (hMG)-stimulated testosterone production were significantly affected by doses of LHRH or LHRHa ranging from 10(-12)--10(-5) M. In addition, adult male rats were treated chronically with once daily injections of LHRH or LHRHa (2 micrograms/rat) or the vehicle for 1--7 days and decapitated 24 h after the last injection, and their testes were removed and weighed. Testicular weights decreased significantly by day 3 and were maximally decreased by day 6. In vitro testosterone production in response to 1--5 mIU human menopausal gonadotropin was markedly impaired (greater than 50%) in cells from rats treated with LHRHa for 2 days or longer and in rats treated with LHRH longer than 3 days. These data indicate that 1) LHRH and LHRHa do not alter in vitro testosterone production by dispersed rat interstitial cells and 2) interstitial cells of rats pretreated with LHRH and LHRHa exhibited impaired in vitro testosterone production. The data do not, however, rule out a direct effect of LHRH or LHRHa on testicular systems other than those involved in steroidogenesis.

Animals↗
PubMed1980

Hypothalamic amenorrhea in runners of normal body composition.

Three amenorrheic runners of normal body weight, in whom organic disease had been excluded, were found to exhibit: (1) normal body composition, (2) low baseline concentrations of serum LH and normal concentrations of FSH, (3) normal to hyper-responsiveness of LH and FSH to GnRH testing, and (4) normal and possibly increased frequency of LH pulsations. In one of the 3 runners, the administration of naloxone was followed by a pronounced increase in the amplitude of the LH pulsations.

Adolescent↗
PubMed1979

Tissue culture studies on human pituitary tumours: long term release of anterior pituitary hormones into the culture medium.

A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.

Acromegaly↗
PubMed1978

Characterization and application of a radioimmunoassay for reduced, carboxymethylated human luteinizing hormone alpha-subunit.

We have established a double antibody RIA using a rabbit antiserum prepared against reduced, carboxymethylated (RCXM) human LH alpha-subunit, with RCXM-alpha as tracer and standard. This antiserum did not cross-react with any native gonadotropins or subunit, and reacted only weakly with RCXM-alpha. A tryptic digest of RCXM alpha-subunit was completely reactive, while chymotryptic digestion abolished all immunoreactivity. By testing with separate tryptic fragments, the recognition site could be localized to a segment close to the amino-terminus of the peptide chain. When applied to measurement of serum and urine, an immunoreactive species, parallel to RCXM alpha-subunit by serial dilution, was found in concentrations of 1-2 ng/ml in serum and 3-4 ng/ml in urine. Similar levels of the immunoreactive component were found in conditions of elevated gonadotropins (e.g. pregnancy) as well as gonadotropin deficiency(panhypopituitarism and Kallmann's syndrome). After stimulation with LHRH, no rise was noted at times up to 6 h despite the fact that both LH and LH-alpha were elevated. The data indicate that the sequence-specific antiserum may be detecting an immunoreactive form of alpha-subunit of LH whose kinetics of appearance and disappearance differs from those of the native subunit.

Amino Acid Sequence↗
PubMed1978

LH-RH testing in men with Down's syndrome.

Males with Down's syndrome frequently present incomplete sexual development and are presumed to be sterile. The intent of this study is to clarify the aetiology of diminished sexual function in men with trisomy 21. Single dose LH-RH stimulation tests were performed in 6 men with Down's syndrome. Compared to a control group of 6 mentally retarded, institutionalized males, the subjects with Down's syndrome had markedly elevated basal FSH and slightly elevated basal LH concentrations. The FSH response to LH-RH stimulation was notably increased in the Down's syndrome group, while the LH response showed a lesser increase. Testosterone concentrations were found to be comparable in the two groups. The results are consistent with the clinical assumption that males with Down's syndrome have decreased spermatogenesis and infertility and that their Leydig cell function is less affected.

Adult↗
PubMed1977

Father-to-son transmission of hypogonadism with anosmia: Kallmann's syndrome.

Gonadal and olfactory features of Kallmann's syndrome, usually considered to be inherited as an X-linked recessive trait, were found in a father and son who both had cryptorchidism, hypogonadism, and hyposmia. The father's fertility had been induced with chorionic gonadotropin, leading to the birth of three children. Olfactory and gonadal functions were normal in the mother and two siblings. The father had low basal plasma testosterone and subnormal follicle stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH). The affected son and his healthy brother were prepubertal. Their basal plasma total and free testosterone, serum FSH and luteinizing hormone (LH), and response to LH-RH were similar. The clinical presentation and formal olfactory function studies were considered most helpful for the suggestive diagnosis of Kallmann's syndrome in children. The occurrence of this syndrome in this family is consistent with autosomal dominant inheritance.

Child↗
PubMed1977

Insensitivity of bonnet monkeys to (D-Ala6, Des-Gly10) LHRH ethylamide, a potent new luteinizing hormone releasing hormone analogue in rats and mice.

The Luteinizing Hormone Releasing Hormone (LHRH) activity of (D-Ala6, Des-Gly10) LHRH ethylamide was compared with that of LHRH in oöphorectomized bonnet monkeys by determining serum LH and FSH concentrations at various time intervals after a sc injection of 100 mug of LHRH and either 100 mug or 1 mg of the analogue. Following administration of synthetic LHRH, a significant rise in both serum LH and FSH was observed. In contrast, no discernible change in serum gonadotropin concentrations was noted following injection of the analogue (D-Ala6, Des-Gly10) LHRH ethylamide, previously reported to have greatly increased potency in rats and mice.

Animals↗
PubMed1977

Conversion of radiolabeled human growth hormone into higher molecular weight moieties in human plasma in vivo and in vitro.

Purified human growth hormone (hGH) was iodinated with 131I ([131I]iodo-hGH) and purified on Sephadex G-100. The monomeric [131I]iodo-hGH (mol wt about 20,000 daltons) was injected as a bolus iv in healthy volunteers and plasma obtained at 10, 20, and 40 min. Then continuous infusion with [131I]-iodo-hGH was started and further plasma samples obtained after 120 min when a plateau of immunoreactive hGH (IR-hGH) had been attained. In one individual the bolus injection was followed further to 60 and 120 min. Fresh plasma was immediately chromatographed on Sephadex G-100 and the IR-hGH profiles evaluated. In all instances following iv injection, larger and occasionally smaller immunoreactive moieties than the injected [131I]iodo-hGH appeared. When [131I]iodo-hGH was incubated at 37 C with fresh human plasma from 4 different individuals from 10 to 120 min, the larger molecular weight forms, noted in the in vivo studies, were again demonstrable. Only the monomeric [131I]iodo-hGH was found when [131I]iodo-hGH was incubated at 37 C for 120 min with human serum albumin or gamma globulin.

Adult↗
PubMed1977

Immunoreactive luteinizing hormone, follicle stimulating hormone and their subunits in human urine following gel filtration.

Urine collected from postmenopausal women, normal men, women and children was prepared by vacuum dialysis and kaolin extraction prior to chromatography on Sephadex G-100. Specific radioimmunoassays for LH, alpha subunit, LHbeta, FSH and FSHbeta were utilized to define the elution patterns of the urinary filtrates, extracts, 2nd IRP-HMG and postmenopausal serum. The following findings were obtained: 1) FSH eluted as a distinct immunoreactive peak whereas LH eluted more diffusely, 2) free alpha subunit was present in all urinary preparations, the 2nd IRP-HMG and postmenopausal serum, 3) free FSHbeta but not LHbeta was detectable in postmenopausal urine, and 4) an LHbeta immunoreactive fragment with an approximate molecular weight of 5000 daltons was present in all urinary preparations and the 2nd IRP-HMG but not in postmenopausal serum.

Adolescent↗
PubMed1977

Analysis of biological and immunological activities in the two pools of LH released during constant infusion of luteinizing hormone-releasing hormone (LHRH) in men.

In response to constant infusion of a submaximal dose of LHRH (0.2 microgram/min for 4 hours), luteinizing hormone (LH) was released in a biphasic pattern in 6 normal men. When the in vitro biologic activity of plasma LH was compared to the immunologic activity throughout the response to LHRH, the B/I ratio remained unchanged (3.6 +/- 0.5, mean +/- SE). Thus, in men the biologic activity of stored LH (acutely releasable) is not different from the presumably newly synthesized hormone that is released as the second pool during prolonged LHRH infusion.

Adult↗
PubMed1977

Immunoreactive luteinizing hormone, follicle stimulating hormone and their subunits in tissue culture media from normal and adenomatous, human pituitary fragments.

Fragments from 4 human pituitaries removed at surgery from one gonadectomized man and three women (one with Nelson's syndrome, one with Forbes Albright syndrome and one with chromophobe adenoma) were grown in tissue culture. The tissue culture medium was changed at weekly intervals, pooled and applied to a Sephadex G-100 column for gel filtration. In each eluate luteinizing hormone (LH), follicle stimulating hormone (FSH), alpha subunit and the beta subunits of LH and FSH were measured by specific radioimmunoassays. For comparison the pituitary standard LER 907 was similarly studied. LH and FSH were measurable in all studies. LH eluted over a broad area whereas FSH eluted as a much sharper peak. In all culture media and in LER 907 large quantities of alpha subunit were detected. The beta subunits of LH and FSH were not present in the LER 907 standard. LHbeta subunit was present in the culture medium of the pituitary fragments from the castrated man and from the women with Nelson's syndrome and Forbes Albright syndrome but not in that of the woman with chromophobe adenoma. FSHbeta subunit was detectable only in the latter case.

Adenoma, Chromophobe↗
PubMed1976

Gonadotropin determinations in times 3-hour urine collections during the menstrual cycle and LHRH testing.

The usefulness of timed 3-hour urine collections as a substitute for serum gonadotropin (LH and FSH) determinations during the menstrual cycle and during LHRH testing was examined. The timing of the 3-hour urine collection is not important in mature individuals, since no significant temporal trend was found when aliquots were collected every 3 hours throughout two 24-hour periods in one mature woman. Good correlation was found between serum LH and FSH concentrations and the quantity of LH and FSH in timed 3-hour urine specimens throughout normal, ovulatory menstrual cycles in two women. Studies before and during 51 LHRH stimulation tests in normal men, children, and women during different phases of the menstrual cycle and in patients with a variety of hypothalamic-pituitary-gonadal axis disorders were performed. There was good correlation between the quantity of the gonadotropins in time 3-hour urine collections and the mean serum LH and FSH concentrations before and during the LHRH test. The "response area" for serum LH and FSH also correlated well with the amounts of LH and FSH in the urine collected during this period. Therefore, the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.

Adolescent↗
PubMed1976

Effects of luteinizing hormone releasing hormone (LHRH) upon bioactive and immunoreactive serum LH levels in normal subjects.

The effects of LHRH stimulation upon plasma LH levels measured by bioassay and radioimmunoassay were examined during the normal menstrual cycle, and in normal men and post-menopausal women. After administration of 100 mug LHRH by subcutaneous injection during the early follicular phase, a 2.7-fold rise in bioactive serum LH to 58 +/- 18 mIU/ml at 30-60 min was accompanied by an equivalent rise in immunoreactive LH, with unchanged bio:immuno (B:I) ratio of 0.9 +/ %/- 0.2 (SD). During the late follicular phase, bioactive serum LH rose 8-fold to 258 +/- 120 mIU/ml at 30-180 min, and the B:I ratio was significantly increased from 1.7 to 2.5. During the luteal phase, bioactive LH values rose 8.1-fold to 223 +/- 97 mIU/ml at 30-60 min, with increase in B:I ratio from 1.1 to 1.8. The LHRH-stimulated serum LH levels declined more rapidly in the early follicular phase than during the late follicular and luteal phases. Elevations of circulating LH concentrations following LHRH administration during the normal menstrual cycle were usually accompanied by a significant rise in B:I ratio, except during the early follic ular phase when the LH responses were small and the B:I ratio did not change. After LHRH stimulation of serum LH levels in men and post-menopausal women, relatively small and inconstant elevations of B:I ratio were observed above the basal value of 2.9. Although the B:I ratio was usually close to unity in cycling women, the ratio was from 2 to 3 in men and postmenopausal women, and during LHRH stimulation of normal women at the late follicular and luteal phases of the menstrual cycle. Thus, the increased LH secretion rate of post-menopausal women and LHRH-stimulated cycling women was frequently accompanied by a rise in the B:I ratio. These observations suggest that circulating LH molecules exhibit a relatively higher biological activity during states of increased biosynthesis and release of gonadotropins.

Adult↗
PubMed1976

Endocrine studies during the refeeding of young women with nutritional amenorrhea and infertility.

Serial endocrine studies were performed during the refeeding of a group of nine young women who presented with amenorrhea associated with injudicious dieting. No significant psychopathology was disclosed by the Lanyon Psychological Screening Inventory in any of the patients, six of whom were single and three married and infertile. The mean weight before refeeding was 81.6% of the normal for height. The mean initial serum follicle-stimulating hormone concentration was within the limits of normal for young women of reproductive age, but the serum luteinizing hormone (LH) concentration and the vaginal maturation score were low. As weight was regained, the serum LH concentration increased (the pooled r for LH versus percent normal weight = 0.85) and the vaginal maturation score rose (the pooled r for vaginal maturation score versus percent normal weight = 0.93). When a mean weight of 96.6% of normal was reached after a mean of 5.3 (range, 2 to 11) months of refeeding, spontaneous menses occurred. The initial cycle was ovulatory in two instances and anovulatory in five, as determined by basal body temperature patterns, plasma progesterone concentrations, and endometrial biopsies. With continued weight gain, menstruation became regular and the three married patients conceived.

Adolescent↗