Vasopressin stimulation of acetate incorporation into lipids in a dimethylbenz(a)anthracene-induced rat mammary tumor cell line.
In a preliminary report we described the effects of rat prolactin on the incorporation of [14C]acetate into lipids by a cell line from a dimethylbenz(a)anthracene-induced rat mammary tumor. The characteristics of the response to prolactin were very similar to those described for the normal rat mammary gland; namely, insulin was required for full expression of the response, maximal activity was not seen until 36 hr after the addition of the hormones, and growth hormone was able to elicit the same response. However, we were unable to detect binding of 125I-labeled prolactin to these cells, and furthermore, other more purified prolactin preparations were inactive. Upon further investigation we discovered that the activity resided in a low-molecular-weight fraction of the rat prolactin B-1 preparation and was probably either vasopressin or oxytocin or both. These data suggest the possibility that vasopressin may play a role in rodent mammary tumorigenesis. (+info)
Evidence for a vasopressin system in the rat heart.
Traditionally, a hypothalamo-neurohypophysial system is thought to be the exclusive source of arginine vasopressin (AVP), a potent antidiuretic, vasoconstricting, and growth-stimulating neuropeptide. We have identified de novo synthesis of AVP in the heart as well as release of the hormone into the cardiac effluents. Specifically, molecular cloning of sequence tags amplified from isolated, buffer-perfused, and pressure-overloaded rat hearts allowed the detection of cardiac AVP mRNA. Subsequent experiments revealed a prominent induction of AVP mRNA (peak at 120 minutes, 59-fold, P<0. 01 versus baseline) and peptide (peak at 120 minutes, 11-fold, P<0. 01 versus baseline) in these isolated hearts. Newly induced vasopressin peptide was localized most prominently to endothelial cells and vascular smooth muscle cells of arterioles and perivascular tissue using immunohistochemistry. In addition to pressure overload, nitric oxide (NO) participated in these alterations, because inhibition of NO synthase by Nomega-nitro-L-arginine methyl ester markedly depressed cardiac AVP mRNA and peptide induction. Immediate cardiac effects related to cardiac AVP induction in isolated, perfused, pressure-overloaded hearts appeared to be coronary vasoconstriction and impaired relaxation. These functional changes were observed in parallel with AVP induction and largely prevented by addition of a V1 receptor blocker (10(-8) mol/L [deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin) to the perfusion buffer. Even more interesting, pressure-overloaded, isolated hearts released the peptide into the coronary effluents, offering the potential for systemic actions of AVP from cardiac origin. We conclude that the heart, stressed by acute pressure overload or NO, expresses vasopressin in concentrations sufficient to cause local and potentially systemic effects. (+info)
Central peptidergic neurons are hyperactive during collateral sprouting and inhibition of activity suppresses sprouting.
Little is known regarding the effect of chronic changes in neuronal activity on the extent of collateral sprouting by identified CNS neurons. We have investigated the relationship between activity and sprouting in oxytocin (OT) and vasopressin (VP) neurons of the hypothalamic magnocellular neurosecretory system (MNS). Uninjured MNS neurons undergo a robust collateral-sprouting response that restores the axon population of the neural lobe (NL) after a lesion of the contralateral MNS (). Simultaneously, lesioned rats develop chronic urinary hyperosmolality indicative of heightened neurosecretory activity. We therefore tested the hypothesis that sprouting MNS neurons are hyperactive by measuring changes in cell and nuclear diameters, OT and VP mRNA pools, and axonal cytochrome oxidase activity (COX). Each of these measures was significantly elevated during the period of most rapid axonal growth between 1 and 4 weeks after the lesion, confirming that both OT and VP neurons are hyperactive while undergoing collateral sprouting. In a second study the hypothesis that chronic inhibition of neuronal activity would interfere with the sprouting response was tested. Chronic hyponatremia (CH) was induced 3 d before the hypothalamic lesion and sustained for 4 weeks to suppress neurosecretory activity. CH abolished the lesion-induced increases in OT and VP mRNA pools and virtually eliminated measurable COX activity in MNS terminals. Counts of the total number of axon profiles in the NL revealed that CH also prevented axonal sprouting from occurring. These results are consistent with the hypothesis that increased neuronal activity is required for denervation-induced collateral sprouting to occur in the MNS. (+info)
Why is the retention of gonadotrophin secretion common in children with panhypopituitarism due to septo-optic dysplasia?
Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities. We describe seven patients (four female, three male) who had at least two out of the three features necessary for the diagnosis of septo-optic dysplasia. Four patients had hypopituitarism and yet normal gonadotrophin secretion: one of these also had anti-diuretic hormone insufficiency; three had isolated GH deficiency and yet had premature puberty, with the onset of puberty at least a year earlier than would have been expected for their bone age. In any progressive and evolving anterior pituitary lesion it is extremely unusual to lose corticotrophin-releasing hormone/ACTH and TRH/TSH secretion and yet to retain gonadotrophin secretion. GnRH neurons develop in the nasal mucosa and migrate to the hypothalamus in early fetal life. We hypothesise that the arrival of GnRH neurons in the hypothalamus after the development of a midline hypothalamic defect may explain these phenomena. Progress in spontaneous/premature puberty in children with De Morsier syndrome may have important implications for management. The combination of GH deficiency and premature puberty may allow an apparently normal growth rate but with an inappropriately advanced bone age resulting in impaired final stature. GnRH analogues may be a therapeutic option. In conclusion, some patients with De Morsier syndrome appear to retain the ability to secrete gonadotrophins in the face of loss of other hypothalamic releasing factors. The migration of GnRH neurons after the development of the midline defect may be an explanation. (+info)
Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats with ascites and water retention.
kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention. (+info)
Stimulus-dependent translocation of kappa opioid receptors to the plasma membrane.
We examined the cellular and subcellular distribution of the cloned kappa opioid receptor (KOR1) and its trafficking to the presynaptic plasma membrane in vasopressin magnocellular neurosecretory neurons. We used immunohistochemistry to show that KOR1 immunoreactivity (IR) colocalized with vasopressin-containing cell bodies, axons, and axon terminals within the posterior pituitary. Ultrastructural analysis revealed that a major fraction of KOR1-IR was associated with the membrane of peptide-containing large secretory vesicles. KOR1-IR was rarely associated with the plasma membrane in unstimulated nerve terminals within the posterior pituitary. A physiological stimulus (salt-loading) that elicits vasopressin release also caused KOR1-IR to translocate from these vesicles to the plasma membrane. After stimulation, there was a significant decrease in KOR1-IR associated with peptide-containing vesicles and a significant increase in KOR1-IR associated with the plasma membrane. This stimulus-dependent translocation of receptors to the presynaptic plasma membrane provides a novel mechanism for regulation of transmitter release. (+info)
Resistance to hepatic action of vasopressin in genetically obese (ob/ob) mice.
1. Fatty acid synthesis, measured in the perfused liver of genetically obese (ob/ob) mice with 3H2O or [14C]actate, did not show the inhibition by [8-arginine]vasopressin (antidiuretic hormone) that is observed in livers from normal mice. 2. Hepatic glycogen breakdown in obese mice was stimuulated by vasopressin, but not as extensively as in lean mice. 3. If obese mice received a restricted amount of food, then fatty acid synthesis still did not respond to vasopressin, but glycogen breakdown was fully stimulated. 4. Cholesterol synthesis was not inhibited by vasopressin in livers from obese mice. 5. Vasopressin inhibited fatty acid synthesis in intact lean mice, but not in obese animals. 6. These results suggest that genetic obesity could be due to an inborn error within the mechanisms (other than adenylate cyclase) which mediate responses to extracellular effectors. (+info)
Evidence for calcium inactivation during hormone release in the rat neurohypophysis.
1. A study has been made of the relationship between 45Ca uptake into and hormone release from isolated rat neurohypophyses incubated in vitro. 2. Hormone secretion is triggered by high-K (56 mM) but long exposure to the stimulus does not generate a maintained release of hormone. 3. When hormone release began to wane, addition of Ba of La increased hormone output which suggests that the decline in output did not result from depletion of the neurosecretory granules at the nerve terminals. 4. 45Ca uptake is enhanced in the presence of high-K concentration, but the initial high rate declines during long exposure to the potassium stimulus with a time constant similar to that of the decline in hormone release. 5. After a period of incubation in a K-rich, calcium-free medium, addition of calcium to the medium induced hormone release. The magnitude of this release was dependent on the time of exposure to excess potassium. 6. After inactivation of secretion, mobilization of internal calcium by means of a calcium ionophore increased hormone release. (+info)