Negative feedback control of the lizard adrenal gland by corticosterone and aldosterone

Hypothalamic implants of corticosterone and aldosterone were equally effective in suppressing plasma corticosterone level in the desert iguana, Dipsosaurus dorsalis, 96 hr after implantation.     

Aromatase activity in marsupial brain,ovaries, and adrenals

In contrast to numerous other vertebrate groups in which there is biochemical evidence for aromatase activity in brain tissues, estrogen synthesis was not detectable in the CNS of a North American marsupial, the Virginia opossum. In the present study, the occurrence of aromatase activity in marsupial brain and other tissues was reinvestigated using the Australian species, Macropus eugenii and Trichosurus vulpecula. Following incubation of tissue homogenates with [7-³H]androstenedione and an NADH-NADPH generating system, estrogen products were isolated and finally identified by methylation and crystallization to constant specific activity. No estrogen was detectable in samples of adult brain; however, the brain of wallaby pouch young conformed to the general vertebrate pattern. Not only were small amounts of authentic estrone synthesized, but aromatization was greatest in limbic areas and activity per unit protein in all regions progressively declined with age. The ovaries of Macropus and Trichosurus as well as the adrenals of Macropus were also capable of converting labeled substrate to estrone or estradiol-17β. This study provides the first definitive evidence for synthesis of conventional eutherian estrogens in Metatheria.     

The influence of mammalian and avian gonadotropins on in vitro ovarian steroid synthesis in the turtle (Chrysemys picta).

The synthesis of steroids from 7α[³H]cholesterol and 7α[³H]pregnenolone by turtle ovarian tissues in vitro was studied. Pregnenolone, 17α-hydroxypregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone, estrone, estradiol 17β, estriol, and 16-epiestriol were identified as products. All estrogens were detectable in incubates of preovulatory follicular tissue, but only small quantities of estrone were found in incubates of follicular tissue from postovulatory animals and luteal tissue. The effects of mammalian and avian gonadotropins on the metabolism of tritiated precursors were studied. Both mammalian and avian LH were stimulatory when conversion of cholesterol or pregnenolone to major steroid products was examined. In particular, enhancement of estrogen biosynthesis predominated in preovulatory follicular tissue, whereas increased progestin yield was the major effect in follicular and luteal tissue from postovulatory animals. The effects of FSH were minimal compared to the same dose of LH. Thus, a slight increase in estrogen yield was only noted when preovulatory follicular tissue was incubated with cholesterol and mammalian FSH, and neither mammalian nor avian FSH had an effect on pregnenolone conversion by follicles from postovulatory animals. Prolactin had no effect on luteal progesterone synthesis when used alone, but reduced the stimulatory effect of mammalian LH on progesterone synthesis. 11-Desoxycorticosterone was not found to be a product of the turtle ovary under normal conditions or after in vitro ACTH stimulation.     

The role of cyclic GMP in the regulation of cyclic AMP hydrolysis.

A rat-heart cyclic nucleotide phosphodiesterase has been chromatographically separated from related enzymes and its kinetic properties have been studied. The enzyme can hydrolyze both cyclic AMP and cyclic GMP and has about the same maximum velocity and apparent KM (greater than 10-5 M) for the two nucleotides. Kinetic plots indicate positive cooperative behavior for both substrates. Cyclic GMP at low concentrations is a potent activator of cyclic AMP hydrolysis and this activation, as well as the cooperativity, can be abolished by treatment with solvents or sulfydryl reagents under conditions which do not destroy the catalytic function. A kinetic model for this enzyme is porposed and the physiologic role is discussed.     

Biochemical basis of fat cell insulin resistance in obese rodents and man

It now appears established that glucose utilization in isolated fat cells prepared from adult $\text{ob}\text{ob}$ mice, as well as spontaneosly obese rats, exhibits a markedly impaired responsiveness to insulin compared to controls. In neither case do decreased insulin receptors or a defective insulin effector system contribute significantly to this impaired response. The principal findings that support this conclusion are that (1) the impaired responsiveness of glucose metabolism in these cells is not overcome by addition of supermaximal concentrations of the hormone and (2) the hexose transport activity in these same fat cells is fully sensitive to activation by insulin under conditions where glucose utilization is not. Thus in both model systems the activity of one or more intracellular enzymes involved in glucose metabolism must be decreased and accounts for the defective response. Recent studies on fat cells from the spontaneously obese rat have identified the pentose shunt and fatty acid synthesis as the key inhibited pathways that lead to their inability to utilize glucose at rates comparable to the activity of insulin-stimulated hexose transport. Further studies will be required to identify the altered metabolic parameters that account for the impaired insulin responsiveness in fat cells from the adult $\text{ob}\text{ob}$ mouse. In addition, it is striking that fat cells from young, 4–7-wk-old $\text{ob}\text{ob}$ mice actually exhibit increased responsiveness to the action of insulin on glucose transport and metabolism when their capacity for fatty acid synthesis is exceedingly high. It seems possible that this amplified responsiveness to insulin in these very young $\text{ob}\text{ob}$ mice may be intimately involved in the etiology of this obese syndrome. Experiments on human fat cells in obesity have been contradictory and indicate that dietary intake and age play major roles in determining the responsiveness of glucose metabolism in these cells to insulin. Too little biochemical information is available on these cells to allow definite conclusions with regard to the cellular locus which contributes most to altered insulin responsiveness. However, the few key studies available suggest that, when observed, impaired insulin responsiveness of fat cells from obese humans also reflects altered metabolic activities rather than insulin receptors or the hormone effector system. That these latter cellular components play a major role in the insulin resistance of muscle or liver remains a possibility that future studies must clarify.     

The prehatching development of the thyroid gland of the fathead minnow, Pimephales promelas (Rafinesque)

The prehatching development of the thyroid gland in the fathead minnow, Pimephales promelas, has been studied using histochemical and autoradiographic methods. The thyroid arises as a solid nodular bud from the pharyngeal epithelium at the posterior border of the hyomandibular junction and then grows ventrocaudally into a tractus thyroglossus from which the follicles eventually form. During subsequent development, the follicles exhibit an exponential increase in number, migrate from the subhyoid region, become diffusely distributed throughout the pharynx and at ectopic loci, and show an increase in the size of the follicular lumina with an accumulation of colloid and a decrease in follicular cell heights due to follicular emptying. Autoradiographic studies suggest that thyroid tissue traps and concentrates iodine prior to the appearance of histochemically demonstrable colloid. Histochemical observations suggest that the formation of thyroid follicles is preceded by the secretion of colloid in the intercellular space and into the tractus thyroglossus.     

Thyroid-stimulating hormone and cyclic adenosine 3',5'-monophosphate in the regulation of thyroid gland function.

The initial step in TSH action reflects binding of the hormone to specific receptor sites on the plasma membrane. Such binding has been studied using plasma membranes, homogenates, isolated thyroid cells grown in culture, and thyroid slices. 3-H- and iodinated TSH preparations have been used; the latter have been prepared using both chloramine-T and lactoperoxidase. Some of the discrepancies reported in the literature might reflect the different thyroid and hormone preparations and the variable incubation conditions which have been used. In general, good correlation exists between binding of TSH and activation of adenylate cyclase in thyroid plasma membranes. Data is reviewed related to activation of protein kinase in intact thyroid cells by TSH. Although there is impressive evidence for cyclic AMP mediation of effects of TSH on the thyroid, some data that are inconsistent with this concept are considered, especially in relationship to 32-P incorporation into phospholipid. The role of cyclic GMP in thyroid function is discussed.     

Growth pattern and behavioral traits associated with the development of the obese-hyperglycemic syndrome in mice (ob/ob)

With respect to the development of various reflex responses and the time of eye opening, the postnatal development of obese mice is normal. From the beginning of the second week post partum, low locomotor activity is detectable in genetically obese mice. This is 1 wk before the epididymal adipocytes of genetically obese mice begin to show enlargement compared to the nonobese littermates. Indications were obtained favoring the idea that mutant nurslings are congenitally hyperphagic. The caloric balance of obese mice, from birth till weaning, and its determining factors are discussed.     

Effect of the daily injection of tolbutamide into pregnant rats on the pancreatic insulin content of their offspring

The pancreas of pups born to rats injected daily with tolbutamide (75 mg/kg) throughout pregnancy contained significantly less insulin than those born to saline-injected rats. The difference was no longer statistically significant 5 days after birth. Intraperitoneal injection of the drug caused a transient fall in maternal and probably fetal blood glucose. At the concentration of 200 μg/ml, tolbutamide did not significantly influence insulin release by the rat fetal pancreas in vitro. The reduction of pancreatic insulin in the tolbutamide exposed pups may, therefore, be explained by decreased fetal blood sugar or alternatively by direct inhibition by tolbutamide of insulin synthesis by rat fetal B-cells. These and previous results lead us to question the so-called “B-cytotrophic” effect of sulfonylurea derivatives in normal rodents.     

The role of vasodilator therapy in heart failure

This article has attemped to summarize the current status of the therapeutic use of vasodilator drugs in acute and chronic heart failure. It is apparent from the increasing number of publications in this area that this alternative to more standard forms of therapy is likely to find a permanent and important place in the management of patients with heart disease. It should also be apparent that ideal drugs for the therapy of chronic heart failure are not yet available. Nevertheless, it is probable that such drugs will emerge and become at least as important as the routine use of digitalis in such patients.     

Control of the interrenal gland of the freshwater turtle Chrysemys picta in vivo and in vitro.

Interrenal function was studied in the freshwater turtle Chrysemys picta by competitive protein-binding analysis of plasma corticosterone in vivo and corticosterone synthesis by interrenal cell suspensions in vitro. Although circulating levels of corticosterone in intact, unanesthetized turtles (0.22 μg/100 ml) are lower than in other vertebrates, hypophysectomy reduced and ACTH increased these levels. Synthetic ACTH_1–24 was more potent in vivo than pACTH, and in vitro 10–1000 pg/ml gave a log dose increase in corticosterone production. Interrenal cell suspensions were also responsive to crude homogenates of turtle pituitary. Bleeding was a potent stimulus to interrenal secretion in vivo mediated in part via endogenous corticotropin release.     

The role of calcium and cyclic nucleotides in alpha-amylase release from slices of rat parotid: studies with the divalent cation ionophore A-23187.

The divalent cation ionophore A-23187 caused a Ca-2+-dependent increase in alpha-amylase release from slices of rat parotid gland. The effect of A-23187 on alpha-amylase release was not caused by release of endogenous agonists since l-propranolol, phentolamine, and atropine had no effect. The magnitude of alpha-amylase release caused by A-23187 was small compared to the effect of isoproterenol. In this respect it more closely resembles the action of cholinergic and alpha-adrenergic agonists on alpha-amylase release. A-23187 inhibited the increase in the level of parotid adenosine 3,5'-monophosphate caused by isoprotrenol. The inhibitory effect required incubation of the slices with the ionophore before the addition of isoproterenol. The ionophore also caused a Ca-2+-dependent increase in the level of guanosine 3',5'-monophosphate (cyclic GMP). Theophylline enhanced the effect of A-23187 on the level of cyclic GMP. These results emphasize the role of Ca-2+ in the regulation of parotid cyclic nucleotide levels. Since the effects of the ionophore depended on the presence of Ca-2+, it is possible that some of the effects of agonists on parotid gland physiology are secondary to an action on intracellular Ca-2+ distribution.     

Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women: I-Lipid physiology.

To evaluate the effect of contraceptive steroids on endogenous glucagon and insulin secretion, theta-arginine was infused intravenously in normal young women before and during selective steroid treatment. The effect of the combination of an estrogen derivative (mestranol), plus norethindrone (Norinyl, Syntex) was compared to the effect of ethinyl estradiol alone and to norethindrone alone. All three steroid schedules resulted in suppression of aminogenic insulin secretion. However, glucagon secretion was reduced only with ethinyl estradiol alone or the combination of mestranol plus norethindrone. In accordance with previous reports, treatment with an ethinyl estradiol derivative alone or in combination with norethindrone resulted in a tendency for elevated serum lipid concentration, while norethindrone alone resulted in a significant reduction in serum lipid concentration. These observations suggest an inverse relationship between aminogenic glucagon secretion and serum lipid concentration as influenced by contraceptive steroids. It is suggested that the metabolic effects of these steroids may be mediated in part by the associated alterations in pancreatic hormone secretory capacity.