Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the mechanisms by which estrogen hormones influence the vascular system, the metabolism of these hormones and the functionality of estrogen receptors were characterized in rat aortic smooth muscle cells from secondary cultures, a widely studied model of vascular biology. Aromatase, estradiol-17 beta-hydroxysteroid dehydrogenase and 17-ketoreductase enzyme activities were demonstrated in these cells. The presence of functional estrogen receptor could also be demonstrated by estrogen-induced transactivating ability in transfection experiments using the luciferase gene reporter and an estrogen responsive element as transcriptional enhancer although the amplitude of the response was only in the range of 140 to 150%. Immunocytochemical analyses, using monoclonal antibodies that recognize epitopes in the A/B domain of the molecule, showed a predominant cytoplasmic localization of these estrogen receptors, even after estrogen addition to the culture medium. Western blot analysis using antibodies that recognize epitopes in the A/B or F domain gave a mol wt of 67,000. Analysis of the estrogen receptor messenger RNA showed that there was no deletion of the proto-signals for nuclear accumulation. The aromatase and dehydrogenase activity results, coupled with the estrogen receptor immunological, RNA analysis, and transfection data strongly support the contention that rat aortic smooth muscle cells are estrogen target cells. This in vitro model is convenient for studying the mechanisms of action of estrogen hormones that seem very peculiar in this cell population.
Atrial natriuretic peptide (ANP) specifically stimulates particulate guanylate cyclase, and cyclic guanosine monophosphate (cGMP) has been recognized as its second messenger. Spontaneously hypertensive rats (SHR) have elevated plasma ANP levels, but manifest an exaggerated natriuretic and diuretic response to exogenous ANP when compared to normotensive strains. In isolated glomeruli, the maximal cGMP response to ANP corresponds to a 12-to 14-fold increase over basal levels in normotensive strains (Wistar 13±2; Wistar-Kyoto 12+2;Sprague-Dawley 14±2) while a maximal 33±3-fold elevation occurs in SHR (P < 0.001). This hyperresponsiveness of cGMP is reproducible in intact glomeruli from SHR from various commercial sources. Furthermore, this abnormality develops early in life, even before hypertension is clearly established, and persists despite pharmacological modulation of blood pressure, indicating that it is a primary event in hypertension.In vitro studies have revealed a higher particulate guanylate cyclase activity in membranes from glomeruli and other tissues from SHR. This increase is not accounted for by different patterns of ANP binding to its receptor subtypes between normotensive and hypertensive strains, as assessed by competitive displacement with C-ANP'02-121, an analog which selectively binds to one ANP receptor subtype. The hyperactivity of particulate guanylate cyclase in SHR and its behavior under basal, ligand (ANP), and detergent-enhanced conditions could be attributed either to increased expression or augmented sensitivity of the enzyme. Radiation-inactivation analysis does not evoke a disturbance in the size of regulatory elements normally repressing enzymatic activity, while the expression of particulate guanylate cyclase gene using mutated standard of A-and B-receptors partial cDNAs, quantified by polymerase chain reaction (PCR) transcript titration assay, manifests a selective increase of one guanylate cyclase subtype. Our data suggest that in hypertension, genetic overexpression of the ANP A-receptor subtype is related to the exaggerated biological response to ANP in this disease. (J. Clin. Invest. 1993. 92:2499-2508
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.