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P Pearce

Publications and source records attributed to P Pearce.

35 records · Page 2Linked to original sources

Thymic sensitivity to sex hormones develops post-natally; an in vivo and an in vitro study.

In vitro thymic organ cultures were used to examine the effects of the sex hormones estradiol and dihydrotestosterone on thymocytes. In contrast with the marked loss of cortical thymocytes seen in vivo with these hormones, no effect was apparent in vitro even at concentrations up to 10(-6) M. The glucocorticoid dexamethasone caused severe depletion in vivo and in vitro. Thymic androgen and estrogen receptors were determined; in the newborn animals up to 2 wk of age, receptor levels were barely detectable. The possibility of indirect modulation of thymic function by steroids in vivo was investigated by culturing thymic lobes in media containing serum from animals treated with these hormones. Only sera from dexamethasone-injected animals caused changes in cell size, number, viability, or phenotype in the culture system. The mechanism for the previously reported effects of sex steroids on the neonatal thymus therefore remains to be elucidated.

Aging↗

Dexamethasone induces different cellular protein synthetic responses in PNA+ and PNA- mouse thymocyte subpopulations.

Thymocytes from adrenalectomized BALB/c male mice were separated by peanut agglutination (PNA) into cortical, corticosensitive, PNA+ cells and larger, medullary, corticoresistant, PNA- cells; the extent of cross-contamination of PNA+ and PNA- cells, and vice versa, was checked by flow microfluorometry. Glucocorticoid receptor profiles were established with 3H-dexamethasone as probe; no differences in receptor affinity or cellular concentration, or in cytoplasmic and nuclear compartmentalization were seen between PNA+ and PNA- cells. On two-dimensional gel electrophoresis, PNA+ and PNA- thymocytes from oil-injected (control) adrenalectomized mice showed patterns of incorporation of 35S-methionine into protein that differed in at least 12 spots, as revealed by autoradiography. PNA+ and PNA- cells from mice treated with submaximal (6 micrograms/day) or near-maximal thymolytic doses of dexamethasone (20 micrograms/day) were also examined by two-dimensional gel electrophoresis. Both PNA+ and PNA- cells showed substantial, overlapping dexamethasone-induced changes in protein synthetic profiles.

Animals↗

Cytoplasmic steroid receptors in ovarian tumours.

Cytoplasmic oestrogen receptors were measured in 40 primary and four secondary ovarian tumors; of these, 43 tumors were also analysed for cytoplasmic progesterone receptors and 34 tumours for cytoplasmic androgen receptors. Serous tumours were significantly more likely to be oestrogen-receptor positive than mucinous tumours, but the incidence of positive progesterone and androgen receptors was similar in serous, mucinous and endometrioid tumours. The mean oestrogen receptor content of serous tumours was significantly higher than that of endometrioid tumours. Well-differentiated epithelial tumours were significantly more likely to be oestrogen-receptor and progesterone-receptor positive than less differentiated epithelial tumours. Two granulosa cell tumours were oestrogen-receptor positive and one of these was also progesterone-receptor and androgen-receptor positive. Four normal ovaries were also analysed for receptor content and two were found to be androgen-receptor positive. The presence of cytoplasmic receptors in ovarian tumours may explain their reported response to endocrine therapy.

Cytoplasm↗

Dihydrotestosterone and estradiol deplete corticosensitive thymocytes lacking in receptors for these hormones.

The sex steroids dihydrotestosterone (DHT) and estradiol (E2), were found to deplete the same cortical population of thymocytes as the glucocorticoid dexamethasone (DM) in intact and in adrenalectomized, castrated mice. Although receptors for DM were demonstrated in this cortical population, none were found for E2 or DHT. We suggest that the sex steroids bind to other thymic elements, possibly thymic reticular epithelial cells, which may in turn act secondarily on cortical thymocytes, or their precursors within the thymus.

Animals↗

Androgens and the thymus.

Tritiated dihydrotestosterone ([3H]DHT) binds with high affinity to a single class of limited capacity sites in cytoplasmic preparations from rat and mouse thymus glands. The affinity of these bindings sites for [3H]DHT (Kd at 4 C, 1 nM) and their specificity [methyltrienolone (R1881) greater than DHT greater than testosterone much greater than estradiol = progesterone greater than promegesterone (R5020) much greater than aldosterone = cortisol] are characteristic of androgen receptors in classical target tissues. The affinity of thymic androgen receptors for [3H]DHT did not differ with age, sex, or species; the concentration of androgen receptors was higher in males than females and higher in older compared with younger animals. Castration of male mice was followed by marked (approximately 2-fold) thymic hypertrophy; the concentration of androgen receptors fell to approximately one third the control value as a function of organ weight, but did not change significantly as a function of thymic DNA. Chronic administration of DHT (200 micrograms/day) did not alter thymic weight or androgen receptor levels in intact male mice. In castrate mice, however, the administration of 200 micrograms DHT completely abolished the thymic hypertrophy otherwise seen post castration and significantly increased the total thymic content of androgen receptor. The administration of dexamethasone (0.6-60 micrograms/day for 5 days) caused dose-related thymolysis; on a weight basis, the concentration of androgen receptor rose markedly, suggesting that androgen receptors are confined to the subpopulation of thymocytes relatively resistant to glucocorticoids.

Aging↗

Intimal lesions in rat caudal artery. Ablation, replacement, and receptor studies on the protective effects of estrogen.

The incidence of spontaneous lesions of the intima in the rat caudal artery is significantly higher in male than in female Wistar rats at 12 weeks of age. After gonadectomy at 5 weeks, lesions in both sexes at 12 weeks reach a level intermediate between those seen in age-matched intact males and females. After gonadectomy at 5 weeks, lesions in both male and female rats are unaffected by testosterone administration but are reduced to below female control levels by diethylstilbestrol. In contrast, diethylstilbestrol administration does not significantly reudce lesion incidence in intact male rats. Binding studies provided no evidence of estrogen-binding sites in cytosol from caudal arteries, but heart and kidney cytosols from both male and female rats contain a single class of high affinity (10(-10)M) binding sites with specificity characteristic of estrogen receptors. Longitudinal studies (4-11 weeks of age) provided no evidence for a change in receptor profile as a factor contributing to the increased lesion incidence in mature male rats.

Animals↗

99mTc-imidodiphosphonate: a superior radio-pharmaceutical for in vivo positive myocardial infarct imaging. I: Experimental data.

99mTc-Imidodiphosphonate (99mTc-IDP) was investigated as an agent for nuclear medicine imaging of acute myocardial infarctions. For this purpose a suitable animal model was found. After coronary artery ligation reproducible myocardial infarcts were obtained with 80% of surviving animals. Scans of the myocardial infarcts were recorded with a high resolution gamma camera and good quality images were obtained. 99mTc-IDP ratios for normal and infarcted tissue were calculated and compared with similar data available from other 99mTc-labelled phosphates. With an infarct/normal ratio of 21:1, 99mTc-IDP is so far the best radiopharmaceutical for nuclear medicine imaging of necrosed heart muscle. Images of the myocardial infarcts have been recorded as early as 6 hours after infarction.

Animals↗

High affinity aldosterone binding sites (type I receptors) in rat heart.

1. The use of the receptor stabilizing agent sodium molybdate, and of RU26988 to exclude [3H]-aldosterone binding from Type II glucocorticoid receptors, has enabled the characterization of high affinity Type I aldosterone binding sites in rat atrial and ventricular cytosols. 2. In adult male and female rats the affinity of binding (Kd 4 degrees C) is approximately 1-2 nmol/l for both atria and ventricles; specificity of binding is similar to that for Type I sites in classical aldosterone target tissues (aldosterone = corticosterone much greater than dexamethasone). 3. Levels of atrial Type I sites are higher than the corresponding levels in ventricle in both males and females, whereas for Type II (classical glucocorticoid) receptors the reverse is the case; levels of both Type I and Type II sites fall over the age range examined (40 days-6 months). 4. The physiological function(s) of cardiac Type I sites, and their in vivo mineralocorticoid or glucocorticoid selectivity, remain to be explored.

Adrenalectomy↗