Suppression of aging in mice by the hormone Klotho

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.     

Expression of an exogenous growth hormone gene by transplantable human epidermal cells

Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.     

Release of luteinizing hormone in male mice during exposure to females: habituation of the response

Male mice release luteinizing hormone when exposed for a short time to a female. In this experiment, multiple blood samples were withdrawn by atrial cannulas from tethered males during either continuous or intermittent exposure to nonreceptive females. After an immediate, transient release of luteinizing hormone, continuous exposure to the same female was accompanied by only random, spontaneous elevations in plasma levels of this hormone. Successive presentations of the same female at 2-hour intervals elicited gradually diminishing luteinizing hormone responses. Exposing such unresponsive males to novel, diestrous females, however, dramatically stimulated their release of the hormone. These results demonstrate habituation of a socially induced, neuroendocrine response involving reproductive hormones.     

Amphibian pituitary growth hormone and prolactin: immunochemical relatedness to rat growth hormone

Growth hormone and prolactin were electrophoretically isolated from amphibian pituitaries and then were tested in a radioimmunoassay with labeled rat growth hormone and antiserum to the same hormone. This isolation and purification of the hormones increased the steepness of the slopes of competitive inhibition in this system when compared to those of crude extracts. Both hormones from most species tested showed high immunochemical cross-reactivity, indicating that amphibian growth hormone and prolactin are structurally related to rat growth hormone.     

Arginine vasopressin as a thyrotropin-releasing hormone

Although hypothyroidism (with concomitant increased levels of thyroid-stimulating hormone) has been associated with elevated plasma vasopressin, the role that vasopressin plays in controlling thyroid-stimulating hormone secretion from the adenohypophysis is not understood. In two in vitro pituitary cell systems, vasopressin caused a specific and dose-related release of thyroid-stimulating hormone from cells that was equal in potency to that elicited by thyrotropin-releasing hormone, the primary acknowledged regulator of thyroid-stimulating hormone release. When injected into the hypothalamus, however, vasopressin specifically inhibited the release of thyroid-stimulating hormone. Thus, vasopressin may exert differential regulatory effects on thyroid-stimulating hormone secretion in the hypothalamus and pituitary gland.     

A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.     

An immunological investigation of human pituitary growth hormone

Growth hormone isolated from human pituitaries has been demonstrated to be a good antigen in the rabbit. With the rabbit antiserum to human somatotropin, it is possible to detect as little as 0.1 microg of the hormone by precipitin test. The antiserum was also capable of neutralizing the growth-promoting activity of human somatotropin.     

Juvenile hormone mimics: effect on cirriped crustacean metamorphosis

A synthetic juvenile hormone mimic has been shown to cause premature metamorphosis of the cyprid larva of an acorn barnacle in concentrations as low as 10 parts per billion in filtered seawater. The effect of a juvenile hormone mimic on a crustacean has not previously been demonstrated.     

Proparathyroid hormone: biosynthesis by human parathyroid adenomas

Biosynthesis of a precursor (proparathyroid hormone) to human parathyroid hormone was demonstrated during incubation of tissue from parathyroid adenomas. The proparathyroid hormone is labeled more rapidly than parathyroid hormone during incubation with amino acids labeled with carbon-14 and is progressively converted to the hormone. Apparent differences in the relative rate of conversion of precursor to hormone found in different tumors suggest that proparathyroid hormone may accumulate in some of the tumors and be secreted into the circulation.     

Synthetic polypeptide antagonists of the hypothalamic luteinizing hormone releasing factor

Two analogs of the hypothalamic luteinizing hormone releasing factor modified at the histidine-2 position were tested for biological activity (secretion of luteinizing hormone) in cultures of dispersed rat anterior pituitary cells. The analog in which glycine was substituted for histidine at position 2, [Gly(2)]LRF, behaves as a partial agonist releasing less than 50 percent of the luteinizing hormone secreted at maximum concentrations of the releasing factor, while the analog in which histidine at position 2 is deleted has no significant agonist activity at any of the doses tested. When added to the cultured cells at molar ratios 10(3) to 10(4) times that of the luteinizing hormone releasing factor, both analogs decrease the amount of luteinizing hormone secreted in response to the releasing factor.     

Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones

A polypeptide isolated from porcine hypothalami stimulates the release of both luteinizing hormone and follicle-stimulating hormone from the pituitaries of several species. This polypeptide has been structurally identified as (pyro)Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH(2) and synthesized. The natural and synthetic materials share biological properties. It appears that this peptide represents the hypothalamic hormone regulating the secretion of both luteinizing hormone and follicle-stimulating hormone.     

Primary structures of human pituitary growth hormone and sheep pituitary lactogenic hormone compared

The primary structures of human pituitary growth hormone and sheep pituitary lactogenic hormone have been compared with regard to similarities in their sequence. Three homologous segments in each molecule, comprising approximately 45 percent of either peptide chain, have been found. These two proteins have apparently evolved from a common ancestor molecule.     

Thyrotropin-releasing hormone: biosynthesis by rat hypothalamic fragments in vitro

Biosynthesis of thyrotropin-releasing hormone (L-pyroglutamyl-L-histidyl-L-proline amide) in vitro was studied. Rat hypothalamic fragments were incubated in Krebs-Ringer bicarbonate buffer that contained either (14)C-labeled proline, histidine, or glutamic acid (the three probable precursor amino acids,) and for control purposes each of 16 other naturally occurring amino acids. A number of labeled peptides were synthesized. With the use of synthetic thyrotropin-releasing hormone, detected by the Pauly reagent or with (125)1-labeled thyrotropin-releasing hormone as a marker, thin-layer chromatograms, paper electrophoresis, and carboxymethyl cellulose ion exchange chromatography revealed that only proline, histidine, and glutamic acid were consistently incorporated into peptides associated with the thyrotropin-releasing hormone region. This synthesizing activity was found in stalk median eminence, ventral hypothalamus. and dorsal hypothalamus but not in neural lobe or cerebral cortex. Because the biosynthetic peptide has identical properties with L-pyroglutamyl-L-histidyl-L-proline amide, it is probable that rat thyrotropin-releasing hormone is similar or identical to both bovine and porcine thyrotropin-releasing hormone and that the native material is present in the pyroglutamyl form in tissues.     

Peptides with juvenile hormone activity

Peptide derivatives of juvenile hormone analogs which show substantial hormonal activity for certain insects were prepared. The most active compound, L-isoleucyl-L-alanyl-p-aminobenzoic acid ethyl ester, was up to twice as active as juvabione. Like juvabione, the peptide analog showed selective action on pyrrhocorid bugs.     

Distal conformation of the thyroid hormone 3,5,3'-triiodo-L-thyronine

In the crystal structure of the thyroid hormone, 3,5,3'-triiodo-L-thyronine, the 3' iodine is observed in the distal position, away from the alaninebearing ring of the thyroid hormone. This result had been anticipated from stereochemical and biological activity studies. However, previous observations of structures in which the 3' iodine was proximal had cast some doubt on the stability of the 3' distal conformation. This observation suggests that the relative energies of the two conformers is similar and that perhaps the barrier to rotation is not as great as previously supposed since both the distal and proximal conformers have now been observed in the solid state.     

Infectious and selectable retrovirus containing an inducible rat growth hormone minigene

A growth hormone minigene carrying its natural promoter (237 nucleotides of chromosomal DNA) was stably propagated in a murine retrovirus containing hypoxanthine-guanine phosphoribosyltransferase as a selectable marker. Glucocorticoid and thyroid hormone inducibility was transferred with the growth hormone gene. Recombinant virus with titers of 10(6) per milliliter was recovered. This demonstration that retroviruses can be used to transfer a nonselectable gene under its own regulatory control enlarges the scope of retroviral vectors as potent tools for gene transfer.     

Identification of a thyroid hormone receptor that is pituitary-specific

Three cellular homologs of the v-erbA oncogene were previously identified in the rat; two of them encode high affinity receptors for the thyroid hormone triiodothyronine (T3). A rat complementary DNA clone encoding a T3 receptor form of the ErbA protein, called r-ErbA beta-2, was isolated. The r-ErbA beta-2 protein differs at its amino terminus from the previously described rat protein encoded by c-erbA beta and referred to as r-ErbA beta-1. Unlike the other members of the c-erbA proto-oncogene family, which have a wide tissue distribution, r-erbA beta-2 appears to be expressed only in the anterior pituitary gland. In addition, thyroid hormone downregulates r-erbA beta-2 messenger RNA but not r-erbA beta-1 messenger RNA in a pituitary tumor-derived cell line. The presence of a pituitary-specific form of the thyroid hormone receptor that may be selectively regulated by thyroid hormone could be important for the differential regulation of gene expression by T3 in the pituitary gland.     

Growth hormone responses to melatonin in man

Oral administration of 1 gram of melatonin caused rapid and significant elevations of serum human growth hormone in eight out of nine normal male subjects. The mean (+/- standard error of the mean) of the peak response by growth hormone was 22.9 +/- 4.6 microunits per milliliter. The increased secretion of growth hormone may be due to interaction of melatonin with hypothalamic serotoninergic receptors.     

Atrial natriuretic factor: a hormone produced by the heart

Systematic studies on the significance of the secretory-like morphological characteristic of cardiac atrial muscle cells of mammals led to the finding that these cells produce a polypeptide hormone. This hormone, described in 1981 as atrial natriuretic factor (ANF), is diuretic (natriuretic), hypotensive, and has an inhibitory effect on renin and aldosterone secretion. Thus, ANF probably intervenes in the short- and long-term control of water and electrolyte balance and of blood pressure. Phylogenetically, ANF appears early, suggesting different functions for this peptide in accordance with each species' environment. Knowledge of the properties of the hormone should provide insights into the pathophysiology of important clinical entities and lead to the development of new pharmaceutical products.     

A novel target for antidiuretic hormone in insects

Diuresis in insects is controlled by two antagonistic hormone groups: diuretic hormones, which promote water loss, and antidiuretic hormones, which inhibit it. All known antidiuretic factors act solely to promote fluid reabsorption by the hindgut and do not affect secretion by the Malpighian tubules. In the house cricket, Acheta domesticus, an antidiuretic hormone was found that inhibits fluid secretion by the Malpighian tubules but has no effect on the hindgut. Correlations were found between the density of neurosecretory granules and the presence of antidiuretic hormone in the corpora cardiaca, suggesting that the hormone is released from specific axons. Its release is triggered by dehydration; the hormone is detectable in the hemolymph of water-deprived crickets. These results imply that an unusual mechanism regulates water balance in these insects.