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Biomedical subjects

D Heber

Publications and source records attributed to D Heber.

At least 127 records · Page 7Linked to original sources
PubMed1983

Circulating immune complexes in patients with diabetes mellitus.

Circulating immune complexes (CIC) were detected by the solid phase C1q binding assay in 16% of 103 diabetic patients and by the fluid phase C1q binding assay in 31% of patients as compared to 5% of 58 control subjects for each assay. Plasma glucose determinations revealed that most patients were moderately hyperglycaemic (mean glucose = 264 mg/dl), and thus were not selected for tight metabolic control. All but six patients had elevated levels of plasma insulin, including both the insulin treated and diet treated subgroups. There was no correlation between the presence of CIC detected by either assay and plasma glucose, insulin, or the presence of microangiopathy. Multiple factors must contribute to the increase in CIC in both insulin deficient and insulin resistant diabetics. The role of these various factors remains to be defined.

Adult↗
PubMed1982

Pituitary desensitization and the regulation of pituitary gonadotropin-releasing hormone (GnRH) receptors following chronic administration of a superactive GnRH analog and testosterone.

We recently demonstrated that chronic daily administration of a superactive GnRH analog to intact rats resulted in an initial stimulation of serum LH levels with a subsequent return of LH levels to baseline at a time when testosterone levels were markedly decreased. These data demonstrated pituitary desensitization following chronic GnRH analog treatment. Administration of GnRH analog with a dose of testosterone which did not markedly lower serum LH levels when administered alone prevented the stimulation of LH secretion by analog. The present studies were undertaken to determine the effects of GnRH analog and testosterone administration on the regulation of pituitary GnRH receptors. Pituitary GnRH receptor binding was increased by analog treatment alone at 20 days and returned to control levels at 40 and 60 days of treatment in parallel to the observed changes in serum LH, demonstrating that one mechanism by which chronic GnRH analog treatment leads to pituitary desensitization is down-regulation of pituitary GnRH receptors. Testosterone administration alone decreased pituitary GnRH receptor binding. Combined GnRH analog and testosterone administration prevented the increase in pituitary GnRH receptors observed with analog administration alone. These studies demonstrate that change in pituitary GnRH receptor binding correlate with changes in serum LH and that the stimulatory effects of analog administration on LH are sensitive to inhibition by small doses of testosterone.

Animals↗
PubMed1982

Pituitary receptor site blockade by a gonadotropin-releasing hormone antagonist in vivo: mechanism of action.

Administration of a potent gonadotropin-releasing hormone (GnRH) antagonist [Nac-L-Ala1,pCl-D-Phe2,D-Trp3,6]GnRH as a single subcutaneous injection to castrated adult male rats reduced, by more than 90 percent, both serum luteinizing hormone concentrations and specific pituitary GnRH receptor binding. This effect persisted for 24 hours. The dissociation rate of the antagonist from pituitary membrane homogenates was fourfold slower than the dissociation rate of a potent agonist. The prolonged in vivo inhibition of pituitary GnRH receptor binding and luteinizing hormone secretion by the GnRH antagonist may be mediated by the slower dissociation rate of the antagonist from its specific pituitary membrane receptor site.

Animals↗
PubMed1982

Hypogonadism in male patients with metastatic cancer prior to chemotherapy.

Gonadal hormonal function was assessed in 44 adult males with disseminated cancer prior to chemotherapeutic treatment of their cancer by determination of plasma testosterone, free testosterone, and luteinizing hormone (LH) levels. Low values for both testosterone (43% decreased) and free testosterone (66% decreased) were seen in this largely malnourished cancer population, in which 82% of patients were less than 90% of ideal body weight. Four patients of serum testosterone and LH were seen: (a) normal testosterone and normal LH (12 cases); (b) normal testosterone and high LH (13 cases), consistent with early primary hypogonadism; (c) low testosterone and high LH (10 cases), consistent with frank primary hypogonadism; (d) low testosterone and normal or low LH (9 cases), consistent with secondary hypogonadism. Significantly decreased ideal body weight was found in the group with low testosterone and low or normal LH level. We conclude that decreased gonadal hormone secretion is frequently seen in adult males with advanced cancer and malnutrition even prior to chemotherapy treatment.

Body Weight↗
PubMed1981

Gonadotropin-releasing hormone analog and testosterone synergistically inhibit spermatogenesis.

We recently demonstrated that superactive gonadotropin-releasing hormone (GnRH) analogs and testosterone synergistically suppress gonadotropin secretion in castrate rats. We proposed that these two classes of agents used in combination would lead to enhanced suppression of spermatogenesis by synergistically inhibiting gonadotropin secretion. This hypothesis was tested in the present study in which synergistic inhibition of spermatogenesis was produced by combined analog and testosterone treatment. The mechanism of the synergistic action observed differed from that hypothesized in that the analog had both primary inhibitory actions directly on the testis and effects at a pituitary level. The addition of testosterone to the regimen further inhibited spermatogenesis by decreasing the secretion of gonadotropins thereby attenuating the compensatory rise in LH and FSH secretion expected with direct analog inhibition of the testis. These studies demonstrate the potential of combined GnRH analog and testosterone administration as a male contraceptive agent and indicate the complexity of their synergistic interactions.

Animals↗
PubMed1981

Down-regulation of pituitary gonadotropin secretion in postmenopausal females by continuous gonadotropin-releasing hormone administration.

Four normal postmenopausal females were infused with synthetic gonadotropin-releasing hormone (GnRH) iv at a rate of 1 microgram/min for 72 h. Serum LH, FSH, and estradiol were measured every 4 h. LH and FSH levels increased from basal values of 23 +/- 3 and 94 +/- 27 mIU/ml, respectively, to peak values of 50 +/- 5 and 145 +/- 9 mIU/ml at 12 h. Serum LH then fell progressively toward basal levels during the continued iv administration of GnRH. Serum FSH fell below basal levels and remained suppressed between 36-72 h of the study period. Serum estradiol remained at levels less than 25 pg/ml throughout the GnRH infusion. Studies of LH and FSH secretion during the continuous administration of GnRH may be a useful model with which to study paradoxical down-regulation of pituitary gonadotropin secretion.

Female↗
PubMed1980

Male contraception; synergism of gonadotropin-releasing hormone analog and testosterone in suppressing gonadotropin.

Long-term administration of either superactive analog's of gonadotropin-releasing hormone or of testosterone suppresses gonadotropin secretion in male animals and humans. Testosterone administered in combination with gonadotropin-releasing hormone analog further suppresses serum gonadotropin levels in male rats. This observation indicates synergistic activity and suggests that the gonadotropin-releasing hormone analog and testosterone act at independent sites within the hypothalamic-pituitary axis. The primary actions of superactive analog are probably mediated by changes at a postreceptor site in the pituitary gonadotropin-secreting cells.

Animals↗
PubMed1979

Pituitary gland: site of short-loop feedback for luteinizing hormone in the rabbit.

The development of a species specific radioimmunoassay for rabbit luteinizing hormone (LH) has permitted the direct demonstration of LH feedback control of LH secretion (short-loop feedback control). In previous studies we showed that small bolus injections of human LH (hLH) intravenously administered to castrate female rabbits suppressed rabbit LH for 20-30 min. Human LH had no effect on rabbit follicle-stimulating hormone secretion. This control system was responsive to amounts of hLH estimated to be present in blood of eugonadal men and women. These studies were designed to determine whether this feedback control was exerted at a pituitary or hypothalamic level. Two groups of studies were carried out: (a) in vivo studies: Rabbit LH was quantified in the blood of castrated female New Zealand White rabbits receiving either constant hLH perfusion (2.75 IU/min) or saline perfusion, plus a bolus injection of 0.5, 6, or 20 mug of gonadotropin-releasing hormone (GnRH). Human LH decreased the response to 6 and 20 mug of GnRH by 31 and 36%, respectively, and abolished the response to 0.5 mug, GnRH. (b) in vitro studies: Rabbit pituitary slices were incubated in the presence of medium alone, medium plus hLH (25 mIU/ml), medium plus GnRH (20 mug/ml), and medium plus both GnRH and hLH. hLH decreased basal rabbit LH release into the medium and abolished GnRH-stimulated rabbit LH release. hLH had no effect on rabbit follicle-stimulating hormone release. From these results we conclude that a direct and specific feedback control of LH on LH exists at a pituitary level.

Animals↗
PubMed1978

GnRH membrane binding: identification, specificity, and quantification in nonpituitary tissues.

Utilizing biologically active 125I-labeled gonadotropin-releasing hormone (125I-GnRH), specific binding with two affinites [KA (high) = 3.2 x 10(8) M-1, KA (low) = 10(5) M-1] were identified in membrane preparations derived from the 10,800 x g pellet of rat pituitary. GnRH-specific low affinity sites (KA - 10(5) M-1) were identified in liver, spleen, renal cortex, lung, testis, ovary, and cardiac muscle. Hypothalamic tissue demonstrated both high- and low-affinity binding. When 125I-GnRH was bound and dissociated, the labeled GnRH retained fully ability to rebind to fresh membrane preparations. That is, binding was not associated with loss of biological activity of GnRH. However, when unbound 125I-GnRH was exposed to the membrane fraction of liver, almost all receptor binding activity disappeared. The presence of low-affinity binding sites in peripheral tissues raises several possibilities: 1) they act as a simple reservoir mediating metabolic clearance of GnRH; 2) they represent enzyme binding sites involved in degradation of GnRH; 3) they mediate peripheral actions of GnRH; or 4) they are simply a cellular membrane constituent unrelated to target actions of GnRH.

Animals↗
PubMed1978

Improved iodination of peptides for radioimmunoassay and membrane radioreceptor assay.

Generally applicable methods for iodinating and purifying small peptide radiolabels for radioimmunoassay and membrane radioreceptor are described in detail. Resulting improvements in radioreceptor assay and radioimmunoassay, as well as results of analyses of specific activity, separation from unlabeled peptide, and storage characteristics, are presented for luliberin, corticotropin, melanotropin, and calcitonin.

Iodine Radioisotopes↗