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Biomedical subjects

J Osterman

Publications and source records attributed to J Osterman.

54 records · Page 3Linked to original sources
PubMed1979

Effects of epidermal growth factor, fibroblast growth factor and bovine serum albumin on ornithine decarboxylase activity of procine granulosa cells.

Epidermal growth factor, a potent mitrogen for granulosa cells produced a three-fold stimulation of ornithine decarboxylase activity in porcine granulose cells in vitro. Fibroblast growth factor, another compound with mitogenic activity for granulose cells, did not stimulate ornithine decarboxylase. Maximally effective concentrations of a commercial preparation of bovine serum albumin equalled the maximal effect of epidermal growth factor on this enzyme activity. The dominant stimulator(s) in the albumin preparation eluted after bovine serum albumin in gel filtration. At maximally effective concentrations, luteinizing hormone produced substantially greater stimulation than either epidermal growth factor or the bovine albumin preparation. Combinations of saturating doses of any two of these stimulators produced additive effects on enzyme activity.

Animals↗
PubMed1979

In vivo metabolism of progestins. V. The effect of protocol design on the estimated metabolic clearance rate and volume of distribution of medroxyprogesterone acetate in women.

The metabolism of the synthetic progestin, [3H]medroxyprogesterone acetate (MPA), was studied in women using a single injection technique. Computer-implemented analysis was used to calculate the MCR (MCRMPA) and volume of distribution (VoMPA) from the steroid disappearance curve. The value of an objective curve-fitting technique was demonstrated. The effect of protocol design (number and frequency of samples) on these metabolic parameters was evaluated. The estimation of VoMPA was most sensitive to alterations of experimental design and biological variability, while MCR was less easily effected. The MCRMPA of 1668 +/- 146 (SEM) liters/day was lower than that for progesterone but higher than that of another synthetic steroid, dexamethasone. Treatment of women with MPA or aminoglutethimide, two drugs known to increase the rates of testosterone and dexamethasone metabolism, respectively, did not alter MCRMPA. From these observations we conclude 1) with the single injection technique it is difficult to estimate Vo of compounds such as MPA which are rapidly metabolized and 2) the MCRMPA was higher than expected and less susceptible to drug-induced changes than the clearance of other steroids.

Aminoglutethimide↗
PubMed1978

Gonadotropin stimulation of porcine ovarian ornithine decarboxylase in vitro: the role of 3',5'-adenosine monophosphate.

The role of cAMP as a mediator of gonadotropin stimulation of ovarian ornithine decarboxylase (ODC) activity was studied in granulosa cells isolated from small (1--2 mm) porcine ovarian follicles. These cells responded to both FSH and LH with significant increases in intracellular concentration of cAMP. At concentrations of gonadotropins which were saturating for the induction of ODC activity, FSH was a more potent stimulator of both cAMP production and ODC activity than LH. N,O'-Dibutyryl cAMP (1.0--10.0 mM) caused a dose-dependent stimulation of ODC activity which equaled the maximal effect of LH but was significantly less effective than the saturating dose of FSH. 8-Bromo-cAMP was more potent than N,O'-dibutyryl cAMP and as effective as FSH as an inducer of ODC activity. Addition of theophylline, a phosphodiesterase inhibitor, to the incubation medium resulted in a dose-dependent inhibition of ODC activity in both control and gonadotropin-stimulated cells. In contrast, 1-methyl,3-isobutyl xanthine, another phosphodiesterase inhibitor, potentiated effects of both submaximal and maximal effective doses of gonadotropins while producing no effect on basal ODC activity of these cells. The results of this study are consistent with the concept that cAMP can mediate gonadotropin stimulation of ODC in porcine granulosa cells. In addition, this study shows the importance of proper selection of cAMP analogs and phosphodiesterase inhibitors, and their concentration in studying such effects.

1-Methyl-3-isobutylxanthine↗
PubMed1977

The in vivo metabolism of progestins. IV. The metabolic clearance rate and plasma binding of 6alpha-methylpregn-4-ene-3, 20-dione in women.

[3H]6alpha-methylprogesterone (6MP) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methylpregna-1,4-diene-3,20-dione. The metabolic clearance rate of 6MP (MCR6MP) was determined in 6 women by the single injection technique. The plasma MCR6MP was 4047 +/- 298 L/day (59 +/- 15 L/day/kg) which was higher than the MCR of progesterone and medroxyprogesterone acetate (6alpha-methyl-17alpha-hydroxy-pregna-4-ene-3,20-dione acetate). The high clearance was not due to binding or metabolism of 6MP by red cells. Although 6MP was bound to CBG with a lower affinity than progesterone, this could not entirely explain the high MCR6MP. When considered with the reports of progesterone and medroxyprogesterone acetate clearance, the present studies suggest that the 6alpha-substitution of progesterone leads to an increased rate of steroid metabolism in women.

Carrier Proteins↗
PubMed1977

FSH and LH stimulation of ornithine decarboxylase activity: studies with porcine granulosa cells in vitro.

Under defined conditions in vitro FSH and LH caused a dose-dependent stimulation of ornithine decarboxylase (ODC) activity in granulosa cells isolated from porcine ovarian follicles. In cells from small follicles, FSH was at least twice as potent an inducer of the enzyme activity as LH. The cells from medium-sized follicles were more responsive to both hormones than cells from small follicles. In addition, the cells from medium-sized follicles were approximately equally responsive to maximal FSH and LH stimulation. Incubation of cells from either small follicles or medium-sized follicles with maximum effective doses of LH plus FSH caused no additive effects.

Animals↗
PubMedDate not supplied

Regulation of testicular ornithine decarboxylase in vitro. Effect of age, follicle-stimulating hormone, and luteinizing hormone.

We have examined hormonal regulation of ornithine decarboxylase (ODC) activity in decapsulated rat testis, isolated testicular interstitial cells, and purified Leydig cells under defined conditions in vitro. Both immature (15 to 26 days old) and adult (60 to 90 days old) rat testes were employed. Basal (fresh tissue) ODC activity varied widely among rats of the same age but was similar (less than 5% difference) in pairs of testes from the same animal. For this reason, pairs of testes were compared in subsequent in vitro studies. ODC activity of decapsulated testes of adult rats declined (to 25 to 30% of basal) during 4 hours of incubation in Medium 199 + 0.1% bovine serum albumin + 0.1 mM 3-isobutyl-1-methylxanthine at 34 C. The addition of FSH, LH, prolactin, prostaglandin E2, epidermal growth factor, insulin, or 10% fetal calf serum singly or in combination failed to prevent this decline in ODC activity. In contrast, ODC activity of decapsulated testes of immature rats remained stable (versus fresh tissue) during 4 hours of incubation. The addition of FSH (100 ng/ml) caused a small but statistically significant (P less than 0.005) stimulation of the enzyme activity, and 8-bromo cyclic AMP (0.5 mM) mimicked the effect of FSH. In isolated interstitial cells from adult rats, LH stimulated ODC activity in a dose- (10 pg-200 ng/ml) and time-dependent fashion. 8-Bromo cyclic AMP mimicked the effect of LH. Prolactin, FSH, estradiol, insulin, prostaglandin E2, and epidermal growth factor did not alter the enzyme activity. LH also stimulated ODC activity of purified Leydig cells. This study demonstrates for the first time direct in vitro stimulation of rodent testicular ODC activity by gonadotropins and reveals marked age-dependent differences in regulation of this enzyme in vitro.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

The aging Leydig cell. VIII. Protein kinase activity.

The effects of aging on cyclic AMP (cAMP) dependent protein kinase activity of purified Leydig cells were evaluated. Purified Leydig cells from 20-day-, 40-day-, 60-day- and 30-month-old rats were incubated with or without hCG for 1 hour. At the end of incubation, tubes were centrifuged and supernatants were saved for cAMP and testosterone determinations, and the pellets were prepared for protein kinase assay. Basal cAMP levels of Leydig cells from 20-day- and 40-day-old rats were lower than those of 60-day- and 30-month-old rats. In response to hCG stimulation, Leydig cells of 40-day-old rats produced the highest amounts of cAMP, while 30-month-old had the lowest levels. Testosterone responses of 30-month-old rates were also significantly lower than those of 60-day-old mature rats. When cAMP-dependent protein kinase activities were measured, 30-month-old rats had the lowest total kinase activity. These results suggest that reduced protein kinase activity might contribute to the decreased testosterone synthesis of aged rats.

Animals↗
PubMedDate not supplied

Nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) from a family cluster with tropical spastic paraparesis/HTLV-I-associated myelopathy.

We describe nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) proviruses from three symptomatic family members with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) from Tumaco, Colombia. Polymerase chain reaction was used to clone the U3 region, envelope and tax/rex genes of these HTLV-I proviruses from fresh peripheral blood lymphocytes. Sequences in U3, env and tax/rex showed 96.9-99.5% conservation when compared with sequences from HTLV-I clone ATK, and 96.6-100% when compared with each other. The range of sequence divergence within the family was similar to that described between unrelated TSP/HAM patients of the same geographical origin. Certain mutations were present in all three family members, supporting a geographic and/or familial segregation of mutations.

Adult↗
PubMedDate not supplied

Serum lipid physiology and the influence of glaucoma medications.

Understanding the effect of serum lipid levels on risk factors for coronary heart disease and how they are influenced by medical therapy may lead to overall better care of the glaucoma patient. Elevated low-density lipoprotein and total cholesterol levels are major risk factors for heart disease. In contrast, high-density lipoprotein (HDL) is protective for heart disease. beta-adrenergic blockers, a class of medicines used to treat glaucoma, may influence serum lipid levels. Oral nonselective beta-adrenergic blockers reduce HDL cholesterol by 19% and increase triglycerides by 20-40%. Furthermore, topical nonselective beta-adrenergic blockers also decrease serum HDL and worsen the total cholesterol/HDL ratio. However, beta-blockers with intrinsic sympathomimetic activity appear to be lipid neutral. At present, there is no clear clinical evidence to indicate that changes in serum lipids with use of topical beta-adrenergic blockers significantly affect the clinical course of the patient. Little information is available for other classes of medicines used topically to treat glaucoma. However, oral preparations of prostaglandins, alpha-adrenergic agonists, angiotensin-converting enzyme inhibitors, and calcium channel blockers do not adversely affect serum lipid levels. Further study is required on newer glaucoma preparations to determine their specific actions on lipid levels. Additionally, further work is required to understand the significance of not only the adverse effect of beta-adrenergic blockers on lipid levels, but their overall effect on long-term cardiac morbidity and mortality.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[14C]-2-deoxyglucose uptake studies in Leydig cells.

The present study examines several aspects of [14C]-2-deoxyglucose uptake by rat Leydig cells: the characteristics of uptake by Leydig cells and type of inhibition by cytochalasin B, the effect of other drugs on [14C]-2-deoxyglucose uptake, the specificity of the glucose transporter for other substrates and the effect of various hormones. The apparent Km and V for [14C]-2-deoxyglucose were 0.4 mM and 0.17 mumol/min/10(6) cells, respectively. The inhibition of [14C]-2-deoxyglucose by cytochalasin B was competitive in nature, with an apparent Ki of 0.28 microM. Both phloretin and phlorizin (1.0-50 microM) inhibited [14C]-2-deoxyglucose uptake in a dose-dependent manner. Although D-glucose inhibited [14C]-2-deoxyglucose uptake by Leydig cells, L-glucose was ineffective, reflecting the stereospecificity of the glucose transporter for the former substrate. Various hormones, including: insulin, LH, 17 beta-estradiol or growth hormone which have been reported to stimulate glucose uptake in cells from other tissues, had no effect on [14C]-2-deoxyglucose uptake in Leydig cells under the current conditions. It remains to be determined how glucose uptake in Leydig cells is regulated.

Animals↗