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Biomedical subjects

I D Morris

Publications and source records attributed to I D Morris.

At least 109 records · Page 6Linked to original sources
PubMed1982

The release of pituitary gonadotrophins by luteinizing hormone releasing hormone in the intact, castrated and aspermatogenic rat.

The change in serum gonadotrophin concentration in response to synthetic Luteinizing Hormone Releasing Hormone (LHRH - 400 ng i.v.) was investigated under barbiturate anaesthesia in adult male rats either chronically castrated, rendered aspermatogenic by the administration of alpha-chlorohydrin 12-16 weeks previously (to remove inhibin), or treated with vehicle. A single injection of LHRH increased serum LH and FSH concentrations similarly in both intact and aspermatogenic rats. In castrated rats the amount of LH released was much greater and the FSH secretion sustained. A second injection produced a similar increase although a second peak of FSH could not be detected in castrated rats as the FSH level was still elevated. The increase in LH levels was two to three times larger in response to the second injection of LHRH than to the first in all groups. The results do not support the hypothesis that the enhanced gonadotropin response to castration in the aspermatogenic rat is due to increased pituitary sensitivity to LHRH.

Animals↗
PubMed1982

The effect of naloxone on some neuroendocrine responses to limb ischaemia.

The finding that naloxone reverses the arterial hypotension produced by bacterial endotoxin in the rat was confirmed and the effect of naloxone on the responses to another form of injury, limb ischaemia was studied. Naloxone had no effect on the fall in blood pressure and colon temperature or on behaviour and survival after bilateral hind-limb ischaemia. The ambient temperature threshold for the onset of shivering was depressed by limb ischaemia as in untreated rats. The increases in the plasma concentrations of glucose and corticosterone and the decrease in that of prolactin after limb ischaemia were unaltered by naloxone. In control rats naloxone reduced the ambient temperature threshold for the onset of shivering and the plasma prolactin concentration. It is concluded that the endogenous opioids do not play a very significant part in the responses to ischaemic limb trauma.

Animals↗
PubMed1982

Hypothalamic, pituitary and uterine cytoplasmic and nuclear oestrogen receptors and their relationship to the serum concentration of tamoxifen and its metabolite, 4-hydroxytamoxifen, in the ovariectomized rat.

High-affinity oestrogen receptors were measured in the cytosol and nuclei prepared from the hypothalamus, pituitary gland and uterus of the ovariectomized rat up to 16 days after a single dose of tamoxifen or 4-hydroxytamoxifen. Tamoxifen produced a dose-related fall in the concentration of cytosol receptors in the hypothalamus, pituitary gland and uterus. Minimum values were observed after 24 h; cytosol receptor concentrations were restored slowly and only reached expected control values between 4 and 8 days and 2 and 4 days for 7.0 mg/kg and 0.7 mg/kg doses of tamoxifen respectively. The nuclear receptor changes were inversely related to the cytosol receptor changes, except that hypothalamic nuclear receptor concentrations after 0.7 mg tamoxifen/kg were not changed. 4-Hydroxytamoxifen (0.14 mg/kg) depleted cytosol and raised nuclear oestrogen receptors in the pituitary gland and uterus. Receptor concentrations had returned to the expected control values by day 4. Oestrogen receptor concentrations in the hypothalamus were unchanged. The apparent resistance of the receptor system in the hypothalamus to translocation by tamoxifen and 4-hydroxytamoxifen was probably due to the blood-brain barrier since the apparent affinity of tamoxifen for the cytosol receptor was similar for all three tissues (dissociation constant 4 nmol/l). Serum concentrations of tamoxifen and 4-hydroxytamoxifen measured after a single dose of 7.0 mg tamoxifen/kg were maximal after 24 h and undetectable by 4 days, at which time nuclear and cytosol receptor levels were still changed. Concentrations of 4-hydroxytamoxifen were approximately one-third those of tamoxifen. The results suggest that the receptor changes after tamoxifen are not simply related to the serum concentration of tamoxifen and its metabolites and that the retention of ligand within the target tissue may be an important determinant.

Animals↗
PubMed1981

Agonist and antagonist activity of en-clomiphene upon oestrogen-mediated events in the uterus, pituitary gland and brain of the rat.

The oestrogen agonist and antagonist activity of a single dose of en-clomiphene (0.5--50 mg/kg) was studied in peripheral and brain tissue in the 3 week ovariectomized rat. 17 beta-Oestradiol benzoate (100 microgram/kg) or vehicle was injected 24 h after en-clomiphene administration and data collected at 72 h. En-clomiphene produced a dose-related (agonist) fall in body weight and food intake. Agonist action was not observed upon sexual receptivity and prolactin secretion; oestrogen antagonism of these parameters was only seen at the higher doses. The effects of en-clomiphene upon serum LH and FSH were complex, both agonist and antagonist activity being demonstrated in the absence and presence of oestrogen. En-clomiphene was uterotrophic at all doses tested; however, oestrogen antagonism was only seen at the higher doses. Inhibition of the accumulation of uterine luminal fluid at the higher doses of en-clomiphene was a sensitive index of oestrogen antagonism. The results are discussed in relation to previous studies of the effects of en-clomiphene on oestrogen receptors. With the exception of the antagonism of oestrogen-induced sexual receptivity no correlation could be made between biological activity and the status of oestrogen receptors in tissue.

Animals↗
PubMed1981

Time-related effects of en-clomiphene upon central and peripheral oestrogen target tissues and cytoplasmic receptors.

The temporal effects of the oestrogen antagonist en-clomiphene were studied in the 3 week ovariectomized rat for up to 24 days after a single dose of 0.5 or 50 mg/kg. Cytosol binding of [3H]oestradiol was measured in central and peripheral target tissues. One day after treatment both doses of en-clomiphene decreased binding of [3H]oestradiol to similar levels within tissues. In brain cytosols binding of [3H]oestradiol returned to expected control values by 16 days with the exception of the hypothalamic cytosol after treatment with 50 mg/kg which, paradoxically, achieved control levels by 8 days. However, a single-point saturation assay was inadequate for the measurement of high-affinity oestrogen receptors in brain tissue. Uterine binding of [3H]oestradiol returned to control levels by 2 and 16 days after treatment with 0.5 and 50 mg/kg respectively. Replenishment of [3H]oestradiol binding was slower in pituitary cytosol and was achieved by 8 and 24 days after treatment with 0.5 and 50 mg/kg respectively. En-clomiphene was uterotrophic; the maximal increase was at 4 days and 1 day after 0.5 and 50 mg/kg and was sustained, albeit at a lower level, for 4 and 8 days respectively. En-clomiphene at 50 mg/kg increased total uterine DNA 2 days after treatment. Small dose-related sustained increases in weight of uterine luminal fluid were also observed. En-clomiphene had no effect upon serum FSH. Serum LH was decreased only on day 8 after treatment. Serum prolactin was increased to a similar level by both doses of en-clomiphene; however, the maximum was achieved 2 and 16 days after treatment with 0.5 and 50 mg/kg respectively. Rats were tested for sexual receptivity after 50 mg/kg en-clomiphene and increases were detected between 7 and 9 days of treatment. Progesterone facilitated this effect only on days 8 and 9. En-clomiphene produced dose-related falls in food intake and body weight, the latter remaining below the weights of control rats throughout the period studied. It is apparent that the temporal effects of en-clomiphene upon cytoplasmic [3H]oestradiol binding are diverse, replenishment of binding being dependent upon the dose and the tissue examined. In addition, the changes in biological activity as measured by uterine and neuroendocrine effects also appear temporally unrelated to each other and to the binding of [3H]oestradiol. Thus further studies are necessary to elucidate possible differences in tissue oestrogen receptor mechanisms and the mode of action of the oestrogen antagonists.

Animals↗
PubMed1980

Some preliminary observations of the nephrotoxicity of the male antifertility drug (+/-)alpha-chlorohydrin.

(+/-)alpha-Chlorohydrin (80 mg kg-1) given by mouth to group-housed adult male Sprague Dawley rats produced an increase in the weight of the kidneys which persisted for at least 7 days, but there were no deaths. This dose administered to Sprague Dawley rats caged singly killed 3 out of 8 animals. The toxicity was studied in more detail using Wistar rats caged singly in metabolic cages. 4 out of 9 animals died with oliguria and anuria after 120 mg kg-1 (+/-)alpha-chorohydrin, 100 and 120 mg kg-1 (in the surviving animals), produced a loss in appetite and body weight, proteinuria, a dose-related diuresis and an increased water intake. Urinary glucose was dramatically elevated after 100 mg kg-1 but after 120 mg kg-1 the glucosuria was not as marked. By day 7 all parameters were returning to their pre-injection values. A dose of 80 mg kg-1 had no effect upon any of the parameters studied. The results are discussed in relation to the basic biochemical mechanism by which the drug exerts its antifertility action, which is achieved at much lower doses.

Animals↗
PubMed1979

Effect on gonadotrophin secretion of blockage of the ductuli efferentes in the normal and androgen-deprived rat.

Serum LH and FSH concentrations were measured in adult male rats. Blockage of the ductuli efferentes by surgical ligation or treatment with the anti-fertility drug alpha-chlorohydrin did not produce any changes in serum LH or androgen-dependent organ weights. Serum FSH in both groups was significantly raised by 4 days after treatment and remained so throughout most of the experimental period (42 days) but did not attain the values obtained in castrates. The gonadotrophin changes were accompanied by an initial increase in the weight and turgidity of the testes which then became flaccid and atrophied. These changes were similar but not identical after both treatments. Androgen secretion was impaired in adult rats treated with ethylene dimethane sulphonate; serum LH values were similar to those of 14-day castrates, and serum FSH was also elevated but not to the level found in the castrates. Ligation of the ductuli efferentes did not produce any further changes in concentrations of either hormone in spite of the retention of the testicular products within the testes as reflected by an increase in weight. The results are consistent with the view that changes in serum FSH after blockage of the ductuli efferentes are related to disturbances in the production of inhibin from the seminiferous epithelium rather than retention of inhibin with the testicular tubules.

Animals↗
PubMed1978

Differential depletion of cytoplasmic high affinity oestrogen receptors after the in vivo administration of the antioestrogens, clomiphene, MER-25 and tamoxifen.

1 The in vivo actions of the oestrogen antagonists, MER-25 and tamoxifen upon the cytosol oestrogen receptors prepared from amygdala, hypothalamus, pituitary and uterus of rats were studied 24 h after drug administration. 2 There was a dose-related depletion of cytosol oestrogen receptors. However, the uterine and pituitary receptors were consistently affected at a lower dose than were those from the brain. 3 The ratios of the combined central ED50 to the combined peripheral ED50 were clomiphene 169 greater than MER-25 19.2 greater than tamoxifen 2.13. 4 The receptor changes were not related to biological activity monitored by serum luteinizing hormone levels and uterotrophic response. 5 The possible role of these drug effects in the induction of ovulation and future developments are discussed.

Animals↗
PubMed1977

Sex differences in the distribution of cytoplasmic oestrogen receptors in rat brain and pituitary: effects of gonadectomy and neonatal androgen treatment.

High affinity binding of 17 beta-oestradiol was measured in cytosols of hypothalamus, amygdaloid region, pituitary and (in females) uterus of adult male and female rats. There were no differences between intact or gonadectomised male and female animals in any of the tissues in the equilibrium dissociation constants (Kd). The number of available binding sites (n) in brain and pituitary in intact females at metoestrus is higher than at proestrus but only in hypothalamus is n greater than in ovariectomised animals. Binding sites in male hypothalamus, amygdala and pituitary are significantly less than in metoestrous females; the sex difference is seen also in gonadectomised rats but is significant only in pituitary. In all female animals the highest concentration of binding sites in the hypothalamus is in the anterior part and the lowest in the posterior part. The distribution of binding sites and Kd values in adult females treated neonatally with testosterone propionate were not different from those of intact proestrous rats. In intact males the highest level of n was in mid-hypothalamus; after gonadectomy the pattern reverted to that in females. It is suggest that these results support the concept that testicular androgen is conversted in brain to a substance with affinity for cytosol oestrogen receptor.

Amygdala↗
PubMed1977

The specificity of oestrogen receptor in brain, pituitary and uterus.

1 The specificity of oestrogen receptor in rat brain regions (hypothalamus, amygdala and cortex), pituitary and uterus was studied by measurement of the inhibition of 17beta-oestradiol high affinity binding in cytosol, in the presence of unlabelled putative inhibitors of binding. 2 Binding was inhibited only by those of the compounds tested that possessed oestrogen agonist or antagonist activity. The affinities were estimated and the ranking order of the compounds was the same in all tissue sources of cytosol and corresponded to the ranking order of agonist or antagonist potency. 3 There were some significant differences between some of the estimated affinities in different tissues, these being seen most commonly between pituitary and hypothalamus on one hand and uterus on the other. 4 The possibility of heterogeneity of oestrogen receptor is discussed.

Amygdala↗
PubMed1976

Changes in brain, pituitary and uterine cytoplasmic oestrogen receptors induced by oestradiol-17beta in the ovariectomized rat.

The oestrogen specific, high-affinity cytosol receptor receptor (HAR) from amygdala, anterior, middle and posterior hypothalamus, pituitary and uterus was studied in the ovariectomized rat. A single in-vivo injection of oestradiol-17beta produced significant changes in both the tissue HAR concentrations and the apparent dissociation constants (Kd) determined in vitro. Four hours after oestradiol-17beta treatment (20 mug/kg), the HAR concentration was depleted in all tissues except the posterior hypothalamus. A lower dose of oestradiol-17beta (4 mug/kg) produced similar changes in HAR concentration with the exception of those in the amygdala and posterior hypothalamus. Twenty-four hours after oestradiol-17beta, HAR concentrations had returned to pre-injection levels in all tissues except the uterus. The uterine HAR concentrations were raised after both doses of oestradiol-17beta. The apparent tissue cytosol Kd values were decreased by both doses of oestradiol-17beta. The results suggest that brain, pituitary and uterine oestrogen cytosol HARs react to plasma oestrogen in a manner predictable by the steroid receptor hypothesis. The oestradiol-17beta-induced differential effects upon the tissue cytosol concentration may contribute to the overall spectrum of action of oestrogen in the central and peripheral reproductive processes.

Amygdala↗