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Biomedical subjects

A Mariotti

Publications and source records attributed to A Mariotti.

At least 19 recordsLinked to original sources

Protein kinases and the androgen-induced proliferation of accessory sex organ smooth muscle.

The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone-sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP-dependent type I and II protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgenic sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen-induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.

Androgens

Protein-metabolism kinetics and energy-substrate utilization in infants fed parenteral solutions with different glucose-fat ratios.

The relative effect of glucose and lipids on whole-body protein-metabolism kinetics was assessed in seven infants undergoing parenteral feeding. Protein intake was kept constant and nonprotein energy was either provided as glucose alone or as an isoenergetic glucose-lipid mixture according to a randomized crossover trial. Protein metabolism and energy-substrate utilization were assessed by a primed, constant L-[13C]leucine infusion, combined with indirect calorimetry. There was a significant difference in the pattern of energy-substrate utilization according to regime. Protein turnover (11.3 +/- 0.7 vs 9.8 +/- 0.4 g.kg-1.d-1; P less than 0.05), protein breakdown (8.4 +/- 0.6 vs 7.1 +/- 0.4 g.kg-1.d-1; P less than 0.05), and amino acid oxidation rates (2.7 +/- 0.4 vs 1.4 +/- 0.5 g.kg-1.d-1; P less than 0.05) were higher for the glucose than the glucose-lipid treatment, whereas protein-synthesis rates did not significantly differ. These results suggest that the nature of energy substrates delivered to parenterally fed infants may affect protein metabolism.

Calorimetry, Indirect

Desquamative gingivitis: revisited.

Desquamative gingivitis is a clinical condition which can encompass a variety of histopathologies. It has not yet been established whether desquamative gingivitis is a distinct hormone-mediated disease entity or a variety of dermatologic diseases (i.e. pemphigus vulgaris, benign mucous membrane pemphigoid, etc.). In this manuscript the epidemiologic, clinical, histopathologic, immunologic and etiologic aspects as well as possible therapeutic modalities for the management of hormone-mediated desquamative gingivitis are examined.

Estrogens

Characterization of fibroblasts derived from human periodontal ligament and gingiva.

Growth characteristics and macromolecular synthesis of fibroblasts derived from human periodontal ligament (PDLF) and gingiva (GF) have been compared in cell culture. Cells were isolated from explants and plated at 500,000 cells/100 mm culture dish (day 0) with daily changes of culture medium. DNA histograms were obtained by flow microfluorimetric analysis to confirm the growth state of the cell cultures. Human PDLF cultures became confluent at day 6 as determined by cell number and cell cycle analysis while GF were confluent by day 4. Initially, DNA content of logarithmically growing cells was significantly greater in GF cultures; however, when confluent, DNA content and cell number was greater in PDLF cultures. Total protein content in GF was slightly greater than PDLF until day 7 but this difference was not significant. Analysis of collagen and noncollagen protein synthesis revealed a greater trend in noncollagen protein synthesis in the GF cultures compared to PDLF cultures. Analysis of glycosaminoglycans in the culture medium of GF and PDLF revealed similar distributions of components. In the cellular fraction, GF had greater amounts of hyaluronic acid and heparin and lesser amounts of chondroitin sulfates A and C than PDLF cultures. The results indicate that the growth characteristics of PDLF and GF, although similar in many respects, do exhibit specific differences in proliferative rates and macromolecular synthesis. The differences observed in these parameters may be important during in vivo events, such as guided tissue regeneration, where significant functional differences are observed between gingival connective tissue and periodontal ligament connective tissue.

Adult

Recovery of [13C]-bicarbonate as respiratory 13CO2 in parenterally fed infants.

Ten infants on continuous total parenteral nutrition (TPN) were infused with NaH13CO3 for 6 h in order to assess the amount of 13C recovered as breath 13CO2. Protein intake was 2.8 +/- 0.3 g/kg/d and non-protein energy intake 107 +/- 4 kcal/kg/d (447 +/- 18 kJ/kg/d), provided either as glucose alone or as an isoenergetic glucose-lipid mixture. In the five infants receiving glucose as the sole non-protein energy source, total CO2 production (559 +/- 50 mumol/kg/min), natural 13C abundance of breath CO2 (-11.8 +/- 0.6 delta % versus PDB) and basal 13CO2 production (6.1 +/- 0.6 mumol/kg/min) were higher than in the five infants infused the glucose-lipid mixture (465 +/- 30 mumol/kg/min, P less than 0.02; -16.1 +/- 0.5 delta %, P less than 0.01 and 5.0 +/- 0.3 mumol/kg min, P less than 0.02, respectively). There was a good agreement, in the glucose-infused infants, between the net glucose oxidation rate measured by indirect calorimetry (25.6 +/- 2 g/kg/d) and the glucose oxidation rate estimated from the 13C natural abundances of breath CO2 and infused substrates (23.5 +/- 3 g/kg/d). Steady state 13C enrichment of breath CO2 was reached in all infants after 120 min infusion and ranged from 11.0 to 21.5 delta % over baseline. Steady state 13C enrichment was negatively related to total CO2 production (r = -0.72; P less than 0.02). In contrast, steady state 13CO2 production in excess of baseline was only correlated to bicarbonate infusion rate (r = 0.95; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Bicarbonates

Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758).

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY156758; [6-hydroxy-2-(4-hydroxyphenyl)benzo(b) thien-3-yl] [4-(2-1-piperidinyl) ethoxyl] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen-maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration-dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen-induced hyperplastic response of the SVM, whereas no interference with androgen-induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen-sensitive SVE as well as the androgen/estrogen-sensitive SVM. Keoxifene-induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.

Androgen Antagonists

Actions and interactions of estradiol and retinoic acid in mouse anterior prostate gland.

Experiments were designed to define the ability of retinoic acid to block the estrogen-induced metaplasia in the mouse anterior prostate gland (coagulating gland), and to elucidate some of the biochemical correlates of the actions and interactions of these two compounds. In castrated mice, the estrogen-induced metaplasia of epithelial cells consisted of multi-layered, nonpolarized cells, which accumulated to fill the lumen of the acini. Retinoic acid had no discernable effect on epithelial morphology of castrates, but significantly reduced the estrogen-induced metaplasia. Likewise, the estrogen-induced increases in the prostatic wet weight, ratio of ribonucleic to deoxy ribonucleic acids (RNA/DNA) and glycosyltransferases, as well as the decreases in 21,000 and 28,000 Mr soluble proteins were prevented by retinoic acid; the retinoid had no effect on these various parameters when administered alone to castrates. In contrast, the cyclic 3',5'-adenosine monophosphate (cAMP)-dependent phosphorylations at 16,000, 18,000, and 25,000 Mr and the activities of the type II cAMP-dependent kinase were uniformly reduced by both estradiol and retinoic acid. Tests of the action of the anti-estrogen LY-156758 on estrogen and retinoid effects showed that for those parameters on which retinoic acid was anti-estrogenic, LY-156758 was also anti-estrogenic. However, the qualitatively similar effects of retinoic acid and estradiol, which were confined to selected aspects of protein phosphorylation, were not antagonized by LY-156758. It is concluded that in the mouse anterior prostate, retinoic acid has both anti-estrogenic and estrogenic actions, and the latter may occur independently of the estrogen receptor.

Animals

Androgen and estrogen effect on guinea pig seminal vesicle muscle: a combined stereological and biochemical study.

A combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone- or estradiol-treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels. The estrogen-induced increase in muscle weight and DNA content appeared to be due only to hyperplasia of muscle cells and not to a proliferation of fibroblasts or to infiltration by inflammatory cells. In all treatment groups, including the estrogen-treated castrates, more than 95% of the cells in the tissue were smooth muscle cells, and there was no evidence that polyploidy contributed to changes in DNA levels. In addition, in the estrogen-treated muscles, DNA concentration remained high, and the stereologically determined cell size remained low. Therefore, both morphological and biochemical evidence indicate that androgen induces hypertrophy, whereas estrogen induces hyperplasia of muscle cells. The correction of stereological and biochemical data validates the application of stereological cell size determination for smooth muscle cells in organs that hardly can be separated into stromal and epithelial components; eg, the prostate.

Animals

The hormonal maintenance and restoration of guinea pig seminal vesicle fibromuscular stroma.

Using the separated epithelium and muscle preparation of the guinea pig seminal vesicle, we designed studies to investigate the hormonal control of epithelial collagen, muscle collagen and muscle cells. All hormone treatment regimens involved a comparison of the effects of hormone maintenance (homrone treatments initiated on the day of castration) versus hormone restoration (hormone treatments initiated after a castration-induced regression) on these 3 components of the fibromuscular stroma. In the epithelium, castration induced a 35 per cent decline in collagen content, which was either returned to normal by androgen restoration of prevented by androgen maintenance. In all androgen treatment regimens, changes in epithelial collagen correlated with changes in epithelial wet weight, cell number, RNA content and cell size. In contrast, growth of the epithelium was not stimulated by estrogen maintenance or restoration. Castration reduced muscle wet and dry weight, as well as cell size and RNA content, but there was no effect on cell number and collagen content. Androgen maintenance or restoration reversed the castration-induced regression in all parameters and also caused collagen content to increase 35 percent above normal. Estrogen maintenance of castrates sustained wet weight, dry weight and RNA content at normal and stimulated supranormal increases in both collagen content and cell number. Similarly, estrogen restoration induced supranormal increases in collagen content and returned RNA content to normal. However, estrogen's ability to stimulate supranormal increases in cell number and restore wet and dry weight to normal was lost after a castration-induced muscle regression. In summary, components of the guinea pig seminal vesicle fibromuscular stroma have been shown to be sensitive to androgens and/or estrogens. The action of androgen on these tissue components was independent of the state of tissue regression, whereas with the exception of RNA and collagen content all the effects of estrogen were significantly reduced with castration-induced regression of the tissue.

Animals

Collagen and cellular proliferation in spontaneous canine benign prostatic hypertrophy.

Towards defining an animal model for study of cellular as well as extracellular matrix accumulation in human benign hypertrophy (BPH), cell number and levels of collagen and zinc were measured in normal and spontaneously hypertrophied canine prostate glands. The increased gland weight in canine BPH was accompanied by increased contents of DNA, collagen and zinc. Concentrations of collagen and zinc in BPH did not differ from normal. These findings indicate that canine BPH involves true hyperplasia and may represent an overgrowth of normal cellular and extracellular components. Canine BPH may prove to be a useful animal model for study not only of cellular proliferation, but also of the connective tissue and zinc accumulation in the human disease.

Animals

Hormonal control of accessory sex organ fibromuscular stroma.

Using the surgically separated epithelium and muscle preparation of the guinea pig seminal vesicle, quantitative determinations were made of the hormonal sensitivities of three components of male accessory sex organ fibromuscular stroma. The parameters measured were epithelial collagen, muscle tissue cell number, and muscle tissue collagen. Epithelial collagen increased approximately tenfold between one week of age and adulthood. This growth was completely prevented by castration and was sustained at normal levels of maintenance of prepubertal castrates with dihydrotestosterone (DHT). Castration of adult animals reduced epithelial collagen 40%; such reductions were prevented by DHT treatment. Estrogen treatment of adult castrates, either alone or in combination with DHT, had no anabolic effect on the epithelium. In all of these studies, changes in epithelial collagen correlated with changes in epithelial wet weight, DNA content, and RNA/DNA. From 1 week of age to adulthood, growth of seminal vesicle muscle involved marked increases in wet weight, DNA content, RNA/DNA, and collagen content. Increments in all parameters were prevented by prepubertal castration and were sustained at normal levels in castrates by DHT treatment. However, in adult animals, muscle DNA content and collagen levels were insensitive to castration and androgen replacement; only tissue weight and cell size (RNA/DNA) were androgen sensitive. Estrogen treatment of adult castrates caused supranormal increases in muscle DNA and collagen; changes in collagen were irreversible. The effects of simultaneous treatment of DHT and estrogen did not differ from those of DHT alone. Therefore, normal postnatal development of the stromal components, epithelial collagen, muscle cells, and muscle collagen was androgen dependent, but in adult animals, only epithelial collagen retained androgenic sensitivity. Estrogen induced supranormal and irreversible growths in the muscle.

Androgens