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.     

Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro

One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.     

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.     

Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin

Adenyl cyclase from plasma membrane fractions of rat renal cortex or medulla was assayed by measuring conversion of adenosine triphosphate labeled at the alpha-phosphate with (32)P to cyclic 3',5'-adenosine monophosphate labeled with 32P. Parathyroid hormone activated the enzyme primarily in cortex; vasopressin acted primarily in medulla. These experiments support the conclusion that cyclic adenosine monophosphate mediates the action of parathyroid hormone on the kidney and show that parathyroid hormone and vasopressin stimulate adenyl cyclase at anatomically separable areas within the kidney.     

Parathyroid hormone effects in rats treated with diphosphonate

The ability of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP; 40 milligrams per kilogram of body weight per day) to reduce the hypercalcemic effect of parathyroid hormone in thyroparathyroidectomized rats was confirmed. However, treatment with this large dose of EHDP enhanced the hypophosphatemic effect of a low dose of parathyroid hormone (10 international units per100 grams of body weight), apparently by promoting the renal excretion of phosphate. The data suggest that EHDP may have a direct effect on the renal action of parathyroid hormone and, in this way, may also affect vitamin D metabolism by the kidney.     

Soldier determination in ants: new role for juvenile hormone

Topical application of juvenile hormone analog induces soldier development in the ant Pheidole bicarinata. Soldier induction takes place if the juvenile hormone analog is present during a period of sensitivity that occurs during the last larval instar. Control of worker dimorphism seems to be accomplished through control of timing of metamorphosis. The smallest size at which metamorphosis can be initiated is shifted upwardfrom 1.2 to 1.7 millimeters by exposure to the juvenile hormone analog during the sensitive period.     

A parathyroid hormone-like protein from cultured human keratinocytes

Parathyroid hormone-like factors have been found in extracts of tumors associated with humoral hypercalcemia of malignancy, many of which are of squamous epithelial origin. Cultured, nonmalignant human keratinocytes were examined for the production of similar factors. Keratinocyte-conditioned medium from ten cultures stimulated the production of cyclic adenosine monophosphate in clonally derived rat osteosarcoma cells sensitive to parathyroid hormone. Bovine [Nle8,18, Tyr34]PTH-(3-34)NH2, a competitive inhibitor of parathyroid hormone, stopped the adenylate cyclase production stimulated by keratinocyte-conditioned medium, but antisera to parathyroid hormone had no effect on such adenylate cyclase activity. The active component of keratinocyte-conditioned medium has a molecular weight exceeding that of native parathyroid hormone. These characteristics are shared by the parathyroid hormone receptor agonists associated with humoral hypercalcemia of malignancy, which suggests that normal human keratinocytes may produce a factor related to that produced by malignant tumors associated with humoral hypercalcemia of malignancy.     

Parathyroid hormone in plasma in adenomatous hyperparathyroidism, uremia, and bronchogenic carcinoma

The concentration of parathyroid hormone (measured by radioimmunoassay) in plasma of patients with severe chronic uremia is frequently much higher than it is in the majority of cases having adenomatous hyperparathyroidism. igher-than-normal concentrations of parathyroid hormone in plasma are found in a significant percentage of unselected patients with bronchogenic carcinoma.     

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.     

Serum parathyroid hormone in X-linked hypophosphatemia

Serum immunoreactive parathyroid hormone(IPTH) is normal in patients with X-linked hypophosphatemic rickets who are not treated with phosphate salts. Phosphate raises IPTH in these patients. Endogenous IPTH does not influence the existing defect in tubular reabsorption of phosphate in male patients.     

Parathyroid hormone production in vitro by human parathyroid cells transformed by Simian virus 40

Cells froma human parathyroid adenoma were infected with simian virus 40 and maintained through 13 subcultures in monolayer tissue culture. For more than 9 months, these "transformed" cells contimed to produce parathyroid hormone which was identified by radioimmunoassay and density-gradient ultra centrifugation.     

Parathyroid hormone-related protein of malignancy: active synthetic fragments

Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.     

Erratum

In the report "Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro," by N. Horiuchi et al. (11 Dec., p. 1566), the caption for figure 1 was inadvertently omitted. The figure is reprinted below with the caption. [See Fig. 1. in Source PDF].     

Systemic activity of a juvenile hormone analog

The peptidic analog of insect juvenile hormone, ethyl pivaloyl-L-alanyl-p-aminobenzoate with enormous biological activity on the red cotton bug, Dysdercus cingulatus, has pronounced systemic effect in sunflower plants. The compound is absorbed by the plant tissues and appears to be translocated throughout the plant system in active form. There is some evidence that juvenile hormone analogs of other types also have similar systemic effects. The discovery of systemic action should aid in the possible utilization of juvenile hormone analogs in insect control programs.     

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.     

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.     

Ornithine decarboxylase stimulation in rat ovary by luteinizing hormone

In normal albino rats with a 4-day estrous cycle, the activity of ovarian ornithine decarboxylase undergoes a transitory rise on the evening of proestrus and only at that time. The response could be elicited by the administration of either luteinizing hormone or human chorionic gonadotrophin. When antiserum to luteinizing hormone was injected at 2 p.m. on the day of proestrus, the induction of ornithine decarboxylase was blocked, an indication that the enzyme is under luteinizing hormone control. The strategic positioning of the induction of ornithine decarboxylase between the normal release of luteinizing hormone and ovulation impties that putrescine is associated with the ovulatory process, and opens a new avenue of research on the control of ovulation.     

Juvenile hormone regulates butterfly larval pattern switches

Insect color patterns can be very diverse. This variation is also seen among many larval instar stages, which can take on vastly different phenotypes. Young caterpillars of the swallowtail butterfly, Papilio xuthus, are mimics of bird droppings, whereas the fifth larval instar is camouflaged among the leaves of host plants (cryptic pattern). We find that juvenile hormone (JH) titers decrease during the fourth larval instar. Furthermore, treatment with JH analog at the beginning of the fourth instar stage resulted in reproducing the mimetic pattern instead of the usual cryptic one and likewise altered gene expression patterns to that associated with the mimetic pattern. These findings suggest that JH regulates the progressive larval pattern switch of this insect.     

Evidence for parathyroid failure in magnesium deficiency

Serum immunoreactive parathyroid hormone (IPTH) was low to nondetectable in spite of hypocalcemia in a patient with chronic magnesium deficiency. The administration of magnesium led to parallel increases in serum IPTH, serum calcium, and renal phosphate clearance. These findings support the view that magnesium depletion may result in impaired synthesis or release of parathyroid hormone in man, or both.     

Parathyroid secretion: discovery of a major calcium-dependent protein

Bovine parathyroid tissue incubated in vitro secretes a protein that is distinct from both parathyroid hormone and proparathyroid hormone and comprises about 50 percent of the total secreted protein. This protein appears to be an aggregate consisting of two or more subunits of molecular weight 70,000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Although the function of this protein is unknown, the secretion rates of both the protein and parathyroid hormone respond in parallel to changes in the concentration of calcium in the medium.