Search PubMed⌕ Search

Biomedical subjects

P Pearce

Publications and source records attributed to P Pearce.

At least 37 records · Page 2Linked to original sources
PubMed1988

Inhibition of growth of B16 melanoma by glucocorticoids does not result directly from receptor-mediated inhibition of tumour cells.

The ability of dexamethasone (DM) to slow the growth of B16 melanoma in C57B1 mice was confirmed. Inhibition was dose-related and was demonstrated in the use of established tumours as well as initial transplants. Although glucocorticoid receptors (GR) were present in cultured tumour cells, DM did not reduce growth of B16 in vitro, even at high concentration. This dissociation of effect on growth in vivo and in vitro suggests that DM slows B16 tumour growth in vivo by mechanisms other than GR-mediated inhibition of tumour cells.

Animals↗
PubMed1987

High-affinity aldosterone binding in rat liver--a re-evaluation.

The use of sodium molybdate as a stabilizing agent, and a RU26988 to exclude [3H]aldosterone from Type II glucocorticoid receptors, has enabled us to characterize high affinity Type I aldosterone binding sites in rat liver cytosol. In liver cytosols from male rats aldosterone bound with an affinity (Kd-22 degrees C) of 0.6 nmol/l (range 0.3-0.8 nmol/l), and Nmax 1.7 fm/mg protein (s.e.m. = 0.4); specificity of binding was similar to that for Type I sites in classical aldosterone target tissues (aldosterone greater than or equal to corticosterone greater than dexamethasone). Hepatic Type I receptor levels were relatively constant in both male and female rats aged 30-120 days, with levels significantly higher in females. Parallel studies on hepatoma H4 cells showed levels of Type I sites similar to those in normal liver, suggesting a general distribution of such sites throughout liver parenchyma, rather than a concentration in a specific cell type. The function of such Type I sites, and whether or not they are aldosterone-selective in vivo and can thus act as mineralocorticoid receptors, remains to be determined.

Androstanols↗
PubMed1986

Cytosol and nuclear levels of thymic progesterone receptors in pregnant, pseudopregnant and steroid-treated rats.

Cytosol and nuclear levels of progesterone receptors in rat thymus and uterus were compared in mature Sprague-Dawley rats under a variety of physiological (non-oestrus, oestrus, pregnancy) and experimental circumstances (pseudopregnancy, oestrogen administration, oestrogen plus progesterone administration). Cytosols and nuclear extracts were charcoal treated to remove endogenous steroids, and incubated overnight at 4 degrees C with the synthetic progestin [3H]R5020 +/- greater than 100-fold R5020, in the presence of greater than 200-fold RU26988 (a highly specific synthetic glucocorticoid) to exclude tracer from glucocorticoid receptors. In the various states examined, levels of progesterone receptors in the uterus were an order of magnitude higher (350-1300 fmol/mg protein) than in the thymus (40-140 fmol/mg protein). In contrast, considerable parallelism between uterus and thymus was seen in terms of the effects of the various manipulations upon tissue levels of progesterone receptors, and of their distribution between cytosol and nuclear compartments.

Animals↗
PubMed1986

Pulmonary haemodynamics of the yak, cattle, and cross breeds at high altitude.

The pulmonary arterial pressure of Ladakhi yaks, at an altitude of about 4500m, was not significantly different from that found in yaks bred at low altitude. The pulmonary arterial resistance, however, was slightly but significantly increased in the high altitude group. It is concluded that the yak has adapted genetically to high altitude by largely eliminating the hypoxic pulmonary vasoconstrictor response. The pulmonary arterial pressure and resistance were significantly higher in indigenous Himalayan cattle than in the yaks. The dzo (cow X yak) had pulmonary haemodynamics similar to those of the yak. Half of the stols (dzo X bull) had pulmonary haemodynamics similar to those of the yak, while in the other half the findings resembled those in the cow. The results suggest that the genetic attenuation of the hypoxic vasoconstrictor response is transmitted as a simple autosomal dominant.

Altitude↗
PubMed1985

Aldosterone-receptor deficiency in pseudohypoaldosteronism.

Pseudohypoaldosteronism, a syndrome characterized by salt wasting and failure to thrive, usually presents in infancy as high urinary levels of sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. We have investigated this syndrome for the possibility of abnormal Type I or "mineralocorticoid-like" receptors, which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells, including mononuclear leukocytes. We have studied three patients with pseudohypoaldosteronism: the 28-year-old index case in Melbourne (Patient 1) and two siblings in Munich, eight and two years of age (Patients 2 and 3); clinically, Patient 3 had a less severe case than his sister. Percoll-separated control monocytes bound [3H]aldosterone with high affinity (Kd approximately 3 nM) and limited capacity (150 to 600 sites per cell). On repeated examination, no [3H]aldosterone binding was found in monocytes from Patients 1 and 2; in Patient 3, the levels were 62 sites per cell, more than 2 S.D. below those of the control. Levels in the parents of the Munich patients (first cousins) were normal. It appears that pseudohypoaldosteronism is caused by a Type I receptor defect, that the defect may be complete or partial, that transmission may be autosomal recessive, and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues.

Adult↗
PubMed1985

Correlation between cytoplasmic steroid receptors and tumour differentiation and invasion in endometrial carcinoma.

The incidence and levels of cytoplasmic steroid receptors were studied in 155 endometrial carcinomas: oestrogen receptors (ER) were measured in all samples, progesterone receptors (PR) in 148 and androgen receptors (AR) in 118. Well-differentiated adenocarcinomas were significantly more likely to contain ER, PR and AR than were poorly-differentiated tumours, and mean values of ER and PR content were significantly higher in well-differentiated adenocarcinomas than in less-differentiated tumours. Receptor profiles in adenosquamous carcinomas and clear-cell carcinomas were similar to those in adenocarcinomas. Deeply invasive tumours were significantly less likely to be ER, PR or AR positive and, even when positive, such tumours had significantly lower mean levels of ER and PR. Poorly-differentiated tumours were significantly more likely to be ER-negative PR-positive than well-differentiated adenocarcinomas and adenosquamous carcinomas.

Adenocarcinoma↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1980

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↗