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Biomedical subjects

S Reichlin

Publications and source records attributed to S Reichlin.

At least 181 records · Page 10Linked to original sources

Thyrotropin-releasing hormone: abundance in the skin of the frog, Rana pipiens.

Thyrotropin-releasing hormone, a hypothalamic tripeptide that stimulates the secretion of pituitary thyroid-stimulating hormone in mammalian species and is widely distributed throughout the brain of vertebrates, is present in the skin of the frog (Rana pipiens) in concentrations twice that found in the hypothalamus of this amphibian. A skin extract shows biologic activity appropriate to its immunoreactive content. Apart from the brain and spinal cord, immunoreactive thyrotropin-releasing hormone is found only in the blood and retina in significant concentrations. The results imply that frog skin is a huge endocrine organ that synthesizes and secretes this hormone.

Animals↗

"Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas.

We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumor's ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.

Cells, Cultured↗

Somatostatin in human cerebrospinal fluid.

To determine whether somatostatin is found in the hypothalamus and extrahypothalamic brain, we studied autopsy brain tissue by specific immunoassay. The hypothalamus contained the highest concentration (16.7 +/- 2.4 S.D. pg per microgram of protein), with small amounts in brainstem, cerebral cortex, cerebellum, pineal gland and spinal cord. Cerebrospinal fluid of seven neurologically normal persons also contained somatostatin in concentrations ranging from 15 to 55 pg per milliliter. To determine whether brain disease leads to abnormal cerebrospinal-fluid somatostatin, we examined 30 patients with neurologic disease, of whom 20 of 24 with cord or cerebral disease had concentrations above the highest normal level. The wide variety of diseases with somatostatin elevation suggests nonspecific leakage from damaged brain tissue. Cerebrospinal-fluid somatostatin may provide a good index of brain damage. Although correlated statistically with cerebrospinal-fluid protein, somatostatin concentration in five of 24 cases exceeded the upper limit of normal by 3 S.D. while protein was normal.

Adolescent↗

Thyrotropin releasing hormone (TRH) in pineal and hypothalamus of the frog: effect of season and illumination.

The influence of photo-illumination and season on the pineal and hypothalamic content of TRH in the leopard frog (Rana pipiens) was studied. Animals (4-6 in each group) were exposed to constant light or darkness for 72 h and then sacrificed. The pineal and hypothalamus from each frog were extracted for TRH measurement by radioimmunoassay. The experiment was performed in spring, autumn, early winter and mid-winter. In early winter, mid-winter and spring the pineal content of TRH ranged from 0.14-0.70 ng. Significant differences between groups due to season and illumination were recorded. In autumn, mean levels of TRH were 12.95 ng (dark exposed) and 4.19 ng (light exposed)-values 10-20 times higher than at other times of the year (P less than 0.001). The hypothalamic content of TRH ranged from 11.4 ng in spring to 19.5 ng in autumn. Seasonal differences were present, but no effect of light or darkness was found. There was no definite relation between the TRH levels in hypothalamus and pineal. The alteration in pineal and hypothalamic TRH produced by season, and the effect of illumination on pineal TRH content, support the view that TRH has a neuronal function in vertebrates, possibly as a neurotransmitter.

Animals↗

Galactorrhea-amenorrhea syndrome: diagnosis and therapy.

Tests of prolactin regulation in the galactorrhea-amenorrhea syndrome were compared in 18 patients with normal pituitary fossae, seven patients with prolactin-secreting adenomas, and eight normal women. Mean basal prolactin was highest in patients with adenomas and was elevated in those with normal fossae when compared with normal subjects (278 versus 73 versus 10.2 ng/ml). Levodopa, water loading, or luteinizing hormone-releasing hormone testing were of no predictive value in the diagnosis of adenoma. Some patients with adenomas show a greater prolactin response after administration of thyrotrophin hormone-releasing hormone (TRH) than of chlorpromazine, whereas these responses are usually similar in patients with normal fossae. A mean basal prolactin level above 150 ng/ml or an increase of more than 100 ng/ml after TRH administration in a patient with hyperprolactinemia unresponsive to chlorpromazine stimulation strongly suggests a prolactin-secreting tumor. However, because some patients with tumor have prolactin levels below 150 ng/ml, or do not respond to TRH stimulation, or both, functional studies alone cannot permit the diagnosis of all adenomas before the appearance of radiographic changes.

Adenoma↗

Total thyroidectomy for occult familial medullary carcinoma of the thyroid in children.

Experience with 17 children in one kindred with familial medullary carcinoma of the thyroid and pheochromocytoma has demonstrated the utility and validity of periodic provocative testing by calcium infusion or pentagastrin injection in the identification of children with early medullary carcinoma of the thyroid or its premalignant precursor, C-cell hyperplasia. In these 17 patients with two consecutive elevations of calcitonin levels greater than 0.55 ng/ml after stimulation all but one have had MTC or CCH at operation. Total thyroidectomy has been well tolerated and can be performed with an acceptably low incidence of complications in this group of patients.

Adolescent↗

Localization of LHRH in neurons in frog brain (Rana pipiens and Rana catesbeiana).

Hypothalamic extracts from frogs (Rana pipiens) were found to contain a significant quantity of immunoreactive LHRH (3.27 +/- 0.63 ng/hypothalamus) (mean +/- SE) measured by radioimmunoassay. In additional radioimmunoassay studies of gross brain LHRH distribution in R. pipiens and R. catesbeiana, 16% of the total frog brain LHRH was located within the telencephalon-septum-optic chiasm regions while the remainder was distributed within the infundibular hypothalamic-pituitary complex. Immunohistochemical studies using the peroxidase-anti-peroxidase (PAP) unlabeled antibody enzyme technique demonstrated the presence of LHRH selectively within some neuronal perikarya located primarily in the median septal nucleus. Fibers containing immunoreactive LHRH were seen in the vicinity of these neuronal cell bodies and in the medial and lateral septal nuclei. In addition, LHRH-containing fibers extended to the median eminence and posterior pituitary, transversing a course beneath the preoptic recess or through the medial forebrain bundle, and then through the lateral infundibular hypothalamus to enter the median eminence bilaterally. LHRH within the median eminence was located in both the inner subependymal and outer glandular zones. On the basis of earlier physiological studies, it is proposed that this LHRH-peptidergic septo-infundibular pathway is involved in control of cyclic gonadotropin activity in the frog.

Animals↗

Prolactin-releasing factor (PRF) in porcine hypothalamic extract distinct from TRH.

Extracts of porcine hypothalamic fragments (HF) bring about the release of prolactin when injected into estrogen-progesterone pretreated male rats. To determine the extent to which this prolactin-releasing activity (PRA) is attributable to thyrotropin-releasing hormone (TRH) and/or vasopressin (VP), (both hormones capable of releasing prolactin in this preparation), PRA was assayed following destruction of TRH and VP by incubation in rat serum, and after separation on Sephadex G-25 columns. Acetic acid (2N) extracts of HF contain 22 to 27 ng TRH and 650 to 1000 ng of VP per HF as determined by immunoassay. Incubation for 1 h in fresh rat serum degraded 91 to 99% of both TRH and VP. PRA fell after incubation, but was still detectable, indicating residual activity that resisted degradation. Prolactin release responses to HF extracts and to TRH were log-dose dependent, but had different activity slopes. The minimal detected dose of TRH which released prolactin was 10 ng, while minimal effective doses of serum inactivated HF extract contained only 0.6 ng of TRH. Maximum effects with serum-inactivated HF extract were achieved with 2 HF equivalents containing 2.6 ng of TRH. More than 400 ng of TRH were required to give an equivalent PRA response. Sephadex G-25 chromatography of hypothalamic extracts using 2.0 N acetic acid separated a fraction which after treatment with serum to inactivate most TRH present caused marked prolactin release and contained only 0.7 ng of TRH and 0.3 ng of VP per dose. Evidence for a PIF was the demonstration that retarded fractions from the column significantly decreased plasma prolactin levels. The finding of PRA in hypothalamic extracts separate from both TRH and VP is evidence for the existence of a distinct prolactin-releasing factor.

Animals↗

Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma.

The syndrome of familial medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia is inherited as an autosomal dominant trait, and is characterized by development of bilateral and multicentric thyroidal and adrenal medullary tumors. One of the earliest manifestations of adrenal medullary hyperfunction in patients with this syndrome is an increased ratio of epinephrine to norepinephrine in urine. In order to define the morphologic correlates of these early catecholamine abnormalities in a large kindred with familial MTC, a morphometric analysis based on a point-counting system to asses adrenal medullary volume was undertaken. These studies clearly revealed adrenal medullary hyperplasia as reflected by a two- to three-fold increase in medullary volume and weight as compared to age- and sex-matched controls. The increase in total medullary mass resulted from diffuse and multifocal modular proliferations of adrenal medullary cells primarily within the head and body regions of the glands. These results support the hypothesis that the pheochromocytomas in patients with familial MTC may, in fact, represent extreme degrees of nodular hyperplasia of the medulla.

Adrenal Medulla↗