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Biomedical subjects

G Brabant

Publications and source records attributed to G Brabant.

189 records · Page 11Linked to original sources

Changes in testicular hCG binding and Leydig cell function in rats throughout life.

The age dependence of Leydig cell function was investigated in rats from prepuberty (15 days) to senescence (39 months). Serum LH, serum and testicular testosterone were measured by radioimmunoassay. The binding capacity and affinity of LH/hCG receptors were determined by a radioligand receptor assay (hCG/Leydig cells) using 125I-hCG labelled by the lactoperoxidase method. Separation of bound and free 125I and simultaneous concentrations of 125I-hCG was achieved by vacuum ultrafiltration. The biochemical integrity of 125I-hCG tracer was ascertained by various chromatographic procedures. The highest hCG-finding and highest serum LH levels were found during puberty. Serum and testicular testosterone concentrations, however, were maximal in early adulthood. From this period onwards to late senescence hCG-binding changed only slightly, while serum LH and testosterone levels decreased significantly towards late senescence. The study shows that, although hCG binding to the Leydig cell changes characteristically during development, it is minimally affected by aging and cannot therefore be responsible for the reduced androgen biosynthesis in senescence.

Age Factors↗

The TRH-metabolic histidyl-proline-diketopiperazine (DKP) inhibits prolactin secretion in male rhesus monkeys.

Histidyl-proline-diketopiperazine (DKP) -- a stable degradation product of TRH -- has been shown to selectively inhibit prolactin secretion in vitro in rat pituitary tissue. In this study the effects of DKP on serum prolactin in intact and anaesthetized male rhesus monkeys and on TRH-stimulated prolactin levels have been investigated. In conscious monkeys 400 micrograms DKP significantly suppressed prolactin levels by 27%, and under ketamine anaesthesia, serum prolactin was suppressed in a dose-dependent manner by 150 and 400 micrograms DKP. The maximum prolactin response and the cumulative response to TRH (20 micrograms) was significantly and specifically inhibited by 400 micrograms DKP, while the lower dose was without effect. TSH levels were not affected by DKP in any instance. Hence DKP can specifically inhibit prolactin release in the rhesus monkey, and may be discussed as a possible regulatory factor in prolactin secretion.

Animals↗

Stimulation of pituitary and testicular functions with LH-RH agonist or pulsatile LH-RH treatment in the rhesus monkey during the non-breeding season.

Out-of-season male rhesus monkeys were used to compare the effectiveness of pulsatile treatment with LH-RH and administration of LH-RH agonist on testicular function. Treatment with LH-RH agonist (1.0 microgram Hoe 766/day) for 11 weeks resulted in partial stimulation of pituitary and testicular functions. The pituitary LH response to the agonist increased during treatment. Testosterone levels were stimulated to within the normal range and 2 of the 4 treated monkeys produced ejaculates, but sperm counts were below normal. Pulsatile treatment with LH-RH (100 ng every 96 min for 7 days alternating with LH-RH agonist treatment for 7 days) in 2 monkeys induced full testicular activity after 7 weeks. Ejaculations were induced at a time when the rhesus monkey is normally sexually inactive. Seminal characteristics at the end of treatment were similar to values in the normal breeding season. In samples collected from one monkey over a 24-h period before treatment there were no LH spikes and very low testosterone levels. During pulsatile LH-RH treatment distinct LH and testosterone spikes occurred, comparable to those in the breeding season.

Animals↗

Elevated nocturnal profiles of serum leptin in patients with depression.

Leptin, the protein product of the obese (ob) gene, has been suggested to play a role in the regulation of food intake. As depressive episodes are frequently characterized by loss of appetite, reduced food intake and weight loss, altered leptin secretion might also be expected in patients with depression. Therefore, we examined nocturnal (10.00 p.m. to 7.00 a.m.) secretion of leptin, cortisol, ACTH and growth hormone (GH) in a group of 15 patients with depression and age- and sex-matched controls (age range 23-71 years). In addition, the effects of pulsatile administration of growth hormone-releasing hormone (GHRH), thought to be an endogenous antagonist of corticotropin-releasing hormone (CRH), which in turn is believed to play a critical role for the pathophysiology of depression, on nocturnal hormone secretion were assessed. Patients with depression showed a trend towards elevated nocturnal cortisol secretion (F = 3.8, p < 0.05). Nocturnal serum leptin was significantly higher in patients, despite a reported weight loss (F = 8, p < 0.05), but showed the same sexual dimorphism as in controls (F = 20.9, p < 0.01). No significant differences were seen between patients and controls with regard to plasma GH and ACTH. GHRH treatment increased GH secretion in both patients and controls, while the other hormones were not affected. Furthermore, serum leptin was correlated with body mass index (BMI) in controls, but not in patients with depression, supporting an altered regulation of leptin secretion in depressive illness. Finally, we provide some evidence that in young female patients the normal nocturnal leptin surge is blunted. As glucocorticoids can prevent the fasting-induced decline in serum leptin, we propose that hypercortisolism in depression might counteract the reduction in leptin secretion caused by decreased food intake and weight loss. Elevated serum leptin in depression might in turn further promote CRH release, as shown in animals and, hence, contribute to HPA system hyperactivity seen in depression.

Adrenocorticotropic Hormone↗

Neural networks in the analysis of episodic growth hormone release.

Pulsatile secretion of growth hormone (GH) has been observed in healthy controls as well as acromegalic patients. In healthy adults, highly regulated secretory pulses of GH occur 4-8 times within 24 h. This episodic pattern of secretion seems to be related to the optimal induction of physiological effects at the peripheral level. In contrast to normal subjects, acromegalic patients demonstrate an irregular pattern of excessive GH release. This pattern of secretion is responsible for many systemic effects, such as the stimulation of connective tissue growth, cardiovascular and cerebrovascular disease, diabetes mellitus and arthritis. Standard methods for the analysis of pulsatile patterns of hormone secretion did not consistently separate the temporal dynamics of GH release in healthy controls and acromegalic patients under various study conditions. Using the cutting edge technology of artificial neural networks for time series prediction, we were able to achieve significant separation of both groups under various conditions by means of the predictability of their GH secretory dynamics. Improving the predictive results by using a more refined system of multiple neural networks acting in parallel (adaptive mixtures of local experts), we found that this system performed a self-organized segmentation of hormone pulsatility. It separated phases of secretory bursts and quiescence without any prior knowledge of the form of a GH pulse or a model of secretion. Comparing the predictive results for the GH dynamics with those for computer-stimulated stochastic processes, we were able to define the irregular pattern of GH secretion in acromegaly as a random autonomous process. The introduction of neural networks to the analysis of dynamic endocrine systems might help to expand the existing analytical approaches beyond counting frequency and amplitude of hormone pulses.

Acromegaly↗

Pulsatility of 24-hour concentrations of circulating interleukin-1-alpha in healthy women: analysis of integrated basal levels, discrete pulse properties, and correlation with simultaneous interleukin-2 concentrations.

Even though it is widely known that interleukin (IL)-1 alpha acts at the local level, it is still uncertain whether IL-1 alpha is secreted into the circulation and acts at distant sites. We have tried to elucidate this by measuring 24-hour levels of total IL-1 alpha in six healthy female volunteers. Subjects had detectable and pulsatile levels of IL-1 alpha throughout the 24-hour period. The integrated 24-hour IL-1 alpha concentration was 2,367 +/- 753 min x micrograms/l (mean +/- SD), and the integrated pulsatile IL-1 alpha concentration was 553 +/- 260 (25 +/- 10% ot total integrated IL-1 alpha). The mean IL-1 alpha concentration was 1.63 +/- 0.53 micrograms/l, mean pulse frequency/24 h was 12.8 +/- 0.8, mean pulse height was 2.31 +/- 0.52 micrograms/l; mean pulse width was 80.4 +/- 2.3 min, and mean interpulse interval was 105.3 +/- 2.8 min. Total IL-1 alpha levels significantly correlated with those previously reported for IL-2 in the same samples, and IL-1 alpha pulse parameters which are concentration independent were significantly similar to those of IL-2. Furthermore, cross-correlation analysis indicated that in 83% of our subjects (5/6) there was synchronicity of IL-1 alpha and IL-2 levels. IL-1 alpha pulse parameters were in the range reported for hormones which have well-characterized pulsatility, such as growth hormone, luteinizing hormone, follicle-stimulating hormone, cortisol, beta-endorphin, and progesterone. Based on these data we speculate that a pulsatile cytokine cascade may exist in the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Review: recent developments in adrenal surgery.

The improvements of biochemical methods and imaging techniques in the diagnosis of adrenal disorders have changed the surgical management with regard to indication for operation, surgical approach to the adrenals and the extent of resection. This study reviews recent developments in surgical strategy of adrenal disorders based on surgical treatment of 246 patients from 1975 to 1993 at the Medical School of Hannover. Today extraperitoneal incisions are used with increasing frequency in small benign tumours to minimize the surgical trauma. The indication for operation of adrenal incidentalomas should be considered in all patients with hyperfunctional lesions and suspected malignancy. Bilateral total adrenalectomy is attended with the need for life-long adrenocortical supplementation resulting in an impaired quality of life. In this respect MEN 2 patients with bilateral adrenomedullary disease benefit from unilateral or bilateral subtotal resections with preservation of adrenocortical function. In conclusion, adrenal surgery today aims at the reduction of surgical trauma, early diagnosis and treatment of adrenal malignancies, and the preservation of adrenocortical function.

Adrenal Gland Diseases↗