Search PubMed⌕ Search

Biomedical subjects

K Griffiths

Publications and source records attributed to K Griffiths.

At least 235 records · Page 13Linked to original sources
PubMed1977

Early increases in ribonucleic acid polymerase activities of dimethylbenzanthracene-induced mammary tumour nuclei in response to oestradiol-17beta and tamoxifen.

Studies on the mode of action of tamoxifen have shown that this compound ultimately causes regression of mammary tumours induced in female rats by 7,12-dimethylbenz(a)-anthracene, but induces preliminary effects similar to those produced by oestradiol-17beta. Following a single intravenous injection of either substance, a sequence of events was observed which included depletion of cytoplasmic receptor, a concomitant increase in nuclear receptor and a subsequent replenishment of cytoplasmic receptor. Tamoxifen and oestradiol-17beta induced a transient increase in RNA polymerase B activity, followed by increases in RNA polymerase A and, again, RNA polymerase B activity. Tamoxifen, unlike oestradiol-17beta, could not maintain replenishment of cytoplasmic receptor, the increase in RNA polymerase A activity or the secondary rise in RNA polymerase B activity. The basic anti-oestrogenic properties of tamoxifen may be implicit in its inability to maintain oestrogen stimulation, and may be linked to its retention time within the nuclei.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Measurement of free and occupied cytoplasmic and nuclear androgen receptor sites in rat ventral prostate gland.

A method has been developed which allows the estimation of occupied and unoccupied androgen receptor sites in both cytoplasmic and nuclear fractions of rat ventral prostate. The procedure involves precipitation of receptor proteins and incubation of precipitates with labelled 5alpha-dihydrotestosterone. Uptake of 3H-labelled steroid at 0--4 degrees C gives an indication of free receptor, whereas binding at a raised temperature (15 degrees C) allows estimation of occupied receptor. Non-specific binding was measured in the presence of a 100-fold excess of unlabelled 5alpha-dilhydrotestosterone. The exchange method was specific for androgens, and specific binding was detected only in fractions of androgen-dependent tissues. The method can be applied to cytosol, whole nuclei, chromatin and salt-extractable and salt-resistant protein preparations from nuclear fractions, and gives a reliable estimate of total receptor sites when occupied as compared with control measurements of unoccupied sites.

Animals↗
PubMed1976

Circulating hormone concentrations in women with breast cancer.

Multiple plasma-hormone concentrations were measured in sequential plasma-samples from six women with breast cancer and were compared to concentrations in six control women matched for age, years since menopause, and parity. All hormone concentrations in all the women studied were within normal limits. However, within the normal range the plasma-testosterone concentrations in each cancer patient were significantly higher than in each matched control.

Age Factors↗
PubMed1976

The effect of ACTH on plasma testosterone and androstenedione concentrations in patients with prostatic carcinoma.

The effect of Synacthen (beta1-24-corticotrophin) on plasma testosterone and 4-androstene-3, 17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients. The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH.

Adrenocorticotropic Hormone↗
PubMed1976

Plasma steroid and protein hormone concentrations in patients with prostatic carcinoma, before and during oestrogen therapy.

Plasma testosterone, androstenedione, oestradiol-17beta, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were not significantly different in patients with prostatic cancer, with benign prostatic hyperplasia or in patients without prostatic disease. Plasma prolactin concentrations were significantly lower in the patients with benign disease than those with prostatic carcinoma. Endocrine therapy in the form of stilboestrol administration significantly decreased plasma levels of testosterone, oestradiol-17beta, FSH and LH within 7 days of the treatment. After 7 days therapy prolactin levels increased significantly in all patients studied. Changes in growth hormone concentrations were more varied in response to stilboestrol, being elevated in several patients and remaining unchanged in others. Treatment of a few prostatic carcinoma patients who were receiving stilboestrol therapy with CB154, an inhibitor of prolactin secretion, brought an immediate decrease in prolactin levels which was was sustained. Plasma testosterone, androstenedione and growth hormone were unchanged in these patients but a significant decrease in plasma oestradiol-17beta was noted in two patients during CB154 administration.

Aged↗
PubMed1976

In vitro synthesis of steroids by a feminising adrenocortical carcinoma: effect of prolactin and other protein hormones.

The study describes the effects of ACTH, prolactin and other protein hormones on the synthesis and secretion of steroid hormones by tissue from a feminising adrenocortical carcinoma removed from a post-menopausal female. Steroid production by the tissue was determined by high resolution-mass fragmentography and by radioimmunoassay. Prolactin and ACTH stimulated the synthesis of estrogens by the tissue whereas GH, LH and ACTH were more effective than prolactin in stimulating androgen synthesis. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumour tissue indicated a lack of specificity of the membrane receptor sites.

Adenylyl Cyclases↗
PubMed1976

The effect of 2-bromo-alpha-ergocryptine (CB154) administration of the hormone levels, organ weights, prostatic morphology and zinc concentrations in the male rat.

2-Bromo-alpha-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.

Adenylyl Cyclases↗
PubMed1976

Measurement of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma during the perinatal period.

A method is described for the resolution and individual quantitation of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma. The steroids were extracted by solvent partition and separated by LH-20 Sephadex column chromatography. Radioimmunoassay was used for the measurement of 11-deoxycortisol and cortisone and competitive protein-binding for corticosterone and cortisol. The relative levels of these steroids in the plasma of chronically catheterized sheep foetuses from 12 days before birth to term and then in the newborn lamb until 2 days of age are recorded. Cortisol gradually increased from a basal concentration of between 0 - 5 and 3 - 0 mug/100 ml plasma between days 12 and 5 pre partum, and then rose rapidly to 10 mug/100 ml plasma during the last 5 days of pregnancy to reach a maximum during or just after birth. Two days post partum the levels had fallen to approximately 3 mug/100 ml plasma. The mean value for 11-deoxycortisol between days 8 and 3 pre partum was 0 - 4 mug/100 ml plasma and increased in the final days before delivery to 1 - 0 mug/100 ml. Corticosterone initially showed slightly higher levels (approximately 1 - 5 mug/100 ml) in the earlier period of investigation but then fell during the immediate pre-partum period to 0 - 8 mug/100 ml. Cortisone was not detected at any stage of the investigations. The relationship between levels of cortisol and 11-deoxycortisol in foetal plasma and myometrial contractility is shown. An increase in uterine activity was seen to occur at the time that cortisol levels were at their maximum. The 11-deoxycortisol values throughout this particular study remained low. The results are discussed in relation to recorded levels in the adult and to previous studies in vitro with regard to changing steroid biosynthetic enzyme activity.

Animals↗
PubMed1976

Effect of the anti-oestrogen tamoxifen on plasma levels of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol and progesterone in normal pre-menopausal women.

Plasma levels of LH, FSH, prolactin, oestradiol and progesterone were determined daily during two consecutive menstrual cycles in six women volunteers. During the first (control) cycle no treatment was given and normal secretion of these hormones was observed. Oral administration of tamoxifen (20 mg/day), for either 5 or 10 days of the follicular phase of the second cycle, caused no change in either the overall length of the cycle or the time of occurrence of the mid-cycle gonadotrophin surge. There was little difference in the secretion of LH, FSH and progesterone during the control and test cycles. A two- to eight-fold increase in oestradiol levels was observed during test cycle which was most pronounced at the times of mid-cycle and mid-luteal hormone peaks. There was a significant decrease in plasma prolactin levels at mid-cycle but no real difference could be seen during the remainder of the cycle. The data suggest that tamoxifen may act directly on the ovary to stimulate oestradiol release without intermediary gonadotrophin stimulation. As the drug apparently inhibited prolactin secretion even in the presence of high oestradiol levels, an alternative explanation may be that the reduced prolactin concentration permits augmented ovarian stimulation by normal concentrations of gonadotrophins.

Adult↗