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Biomedical subjects

C A Wilson

Publications and source records attributed to C A Wilson.

At least 181 records · Page 10Linked to original sources

Quantitative measurements of retinal edema by specific gravity determinations.

We have quantified retinal edema in rat by specific gravity measurements in vitro. Specific gravity corresponds to tissue water content, which is increased in retinal edema. The gravimetric analysis of retinal edema corresponds well with light and transmission electron microscopy and radiolabelled albumen studies. Specific gravity measurements are the standard method to measure brain edema and are also applicable to the measurement of retinal edema.

Animals↗

The effect of neonatal manipulation of hypothalamic serotonin levels on sexual activity in the adult rat.

5HT and 5HIAA levels were altered in neonatal males and females by treating them with 100 mg/kg p-chlorophenylalanine (PCPA) or 20 mg/kg 5-hydroxytryptophan (5HTP) over eight days 1 to 7 or 11 to 16 of life. Androgenized females (testosterone propionate given on day 1) were also treated over days 1 to 7. In adulthood the effects of these treatments on sexual behaviour were observed. None of the treatments affected feminine sexual behaviour in either sex. Reduction of 5HT activity by PCPA enhanced masculine sexual behaviour in males and potentiated the defeminizing effect of exogenous testosterone in females. Increasing 5HT by 5HTP antagonised the defeminizing effect of exogenous testosterone. These findings indicate that the lower levels of hypothalamic 5HT and 5HIAA seen in the neonatal males may have some physiological importance, since 5HT appears to antagonise the androgenizing and defeminizing effects of testosterone.

5-Hydroxytryptophan↗

Mechanisms by which 5HT stimulates ovulation in the immature rat treated with pregnant mare serum gonadotrophin.

Pregnant mare serum gonadotrophin (PMS) normally induces a pre-ovulatory immunoreactive LH surge followed by ovulation in 27 day old rats provided they weigh more than 60 g; ovulation does not occur in the lighter rats although a pre-ovulatory LH surge can still be measured. 5HT injected into the paraventricular nucleus (PVN) can induce ovulation in these smaller rats treated with PMS and does so without appearing to stimulate extra immunoreactive LH. The LH secreted in the under 60 g PMS-treated rats is a pleiomorphic form since it cannot be detected by cytochemical bioassay, indicating abnormal biological activity, which may account for its failure to induce ovulation. After unilateral injection of 5HT into PVN, the LH was detectable by the bioassay. Injection of 5HT also stimulated the release of growth hormone and prolactin but had no significant effect on the plasma concentration of the gonadotrophins or corticosterone. Since an injection of exogenous GH converted the LH to a fully bioactive form it is suggested that GH is important in inducing the secretion of an "adult' form of LH in the peripubertal rat necessary for first ovulation and that 5HT exerts its ovulatory effect via stimulating the release of this hormone.

Animals↗

Effect of testosterone on gonadotrophin-releasing hormone receptors in the castrated rat: preliminary evidence for a stimulatory effect of testosterone on gonadotrophin function in the male rat.

In the long-term castrated rat the negative feedback effect of testosterone is markedly reduced and the raised levels of plasma LH seen in the castrated animals are not suppressed by physiological concentrations of plasma testosterone. In this study we have measured pituitary gonadotrophin-releasing hormone (GnRH) receptor content as well as plasma and pituitary LH on days 1, 10 and 40 after castration and noted the effect of testosterone replacement on these parameters. We found that the negative feedback effect of physiological concentrations of testosterone on plasma and pituitary LH, pituitary GnRH receptor content and response to exogenous GnRH was attenuated 10 and 40 days after castration. It is suggested that the lack of effect of testosterone in the long-term castrated rat is due to its inability to reduce the pituitary GnRH receptor content. On increasing testosterone to supraphysiological levels, the negative feedback effect was reinstated. We also found that in rats 40 days after castration, physiological and subphysiological concentrations of testosterone significantly increased pituitary GnRH receptor content and this may explain the previous findings that low concentrations of testosterone can enhance the effect of GnRH and increase plasma LH levels.

Animals↗

Effects of hypophysectomy and growth hormone infusion on rat hepatic carbonic anhydrases.

Rat liver exhibits a reversed sexual dimorphism of its two endogenous soluble carbonic anhydrase (CA) isozymes, CA II and CA III. Normal males have hepatic CA III concentrations ten-twenty times those in the female, while female liver contains two-three times more CA II than the male. Hypophysectomy abolishes this sexual differentiation, having no effect on male liver but producing isozyme concentrations in the female liver similar to those in the male. Infusion of a continuous level of GH into male rats induces a female-like isozyme pattern for both CA II and CA III.

Animals↗

Changes in hypothalamic dopamine D-2 receptors during sexual maturation in male and female rats.

We have examined variations in hypothalamic dopamine D-2 receptor levels occurring during sexual maturation in male and female rats, using a [3H]domperidone radioligand binding assay. A major decrease in D-2 receptor levels was observed during sexual development, and was accompanied by the appearance of a sexual dimorphism in receptor levels, which appeared to be the result of neonatal sexual differentiation. These changes may be linked with the alterations in hormone levels which occur during sexual maturation.

Animals↗

Progesterone stimulates sexual behaviour in female rats by increasing 5-HT activity on 5-HT2 receptors.

We have investigated the possibility that there is a correlation between female sexual receptivity and CNS serotonergic activity. In ovariectomized rats primed with a submaximal steroid regime of 2 micrograms oestradiol benzoate (OB) plus 0.2 mg progesterone (P), so that only a proportion were receptive, the 5-hydroxyindoleacetic acid:5-hydroxytryptamine (5-HT) ratio in the hypothalamus was greater in the receptive compared to the non-receptive rats. When rats were primed with 10 micrograms OB alone, there was no difference in 5-HT activity in the receptive and non-receptive animals. Depletion of hypothalamic 5-HT levels by p-chlorophenylalanine methyl ester (PCPA) inhibited behaviour normally induced by OB plus P and this could be reversed by 5-hydroxytryptophan. PCPA had no effect in animals made receptive by OB alone. This indicates that P, but not OB, exerts its stimulatory effect on sexual behaviour via increasing 5-HT activity. Administration of 5-HT into the lateral, but not 3rd ventricle stimulated sexual behaviour and systemic injection of the selective 5-HT1 and 5-HT2 agonists, Ru 24969 and MK 212, inhibited and stimulated behaviour, respectively. It is suggested that 5-HT has a dual effect on female sexual receptivity acting via different systems, the inhibitory tract acting on 5-HT1 and the stimulatory tract on 5-HT2 receptors.

Animals↗

Rat liver carbonic anhydrase I is not sexually dimorphic but is estrogen repressible.

Carbonic anhydrase (CA) isozymes CAII and CAIII are known to exhibit sexual dimorphism in rat liver, and the levels of these isozymes are affected by sex hormones. In this paper we show that the isozyme CAI is present at low levels in rat liver, with no difference in concentration between male and female rats. Estrogen and diethylstilbestrol reduce CAI levels in both sexes.

Animals↗

The effects of isolation, grouping and aggressive interactions on indole- and catecholamine levels and apparent turnover in the hypothalamus and midbrain of the male golden hamster.

Although the golden hamster is widely used for studies on aggression, there have been no previous investigations of the role of biogenic amines in this species. Like the mouse, isolated male hamsters are highly aggressive towards a conspecific while grouped males are relatively unaggressive. Isolated males exhibited no differences in levels of midbrain or hypothalamic serotonin (5HT), 5-hydroxyindole acetic acid (5HIAA) or norepinephrine (NE) compared with grouped males. Nor were there differences in the percentage changes in 5HT or 5HIAA following monoamine oxidase inhibition by pargyline, nor in the percentage fall in hypothalamic NE after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine (AMPT); midbrain NE in isolates (unlike grouped males) did not decline after AMPT administration. The percentage changes in 5HT after pargyline administration were unaffected by fighting, but the expected percentage fall in hypothalamic 5HIAA did not occur in males (either grouped or isolated) taking part in an aggressive interaction; this may be an indication of increased 5HT turnover. The percentage change in NE after AMPT administration was unaffected by fighting. Pargyline administration (70 mg/kg IP) reduced the aggressive response of isolated male hamsters to an intruder while AMPT (200 mg/kg IP) had no significant effect.

Aggression↗

Studies into the dual effects of serotonergic pharmacological agents on female sexual behaviour in the rat: preliminary evidence that endogenous 5HT is stimulatory.

The potential stimulatory and inhibitory effects on female sexual behaviour of five 5HT antagonists and five agents that increase 5HT activity, were noted in ovariectomised rats primed with various steroid regimes such that they were either "receptive" (LQ greater than 50%) or "non-receptive" (LQ less than 50%). The 5HT antagonists cinanserin, mianserin, ketanserin and metergoline all inhibited behaviour in receptive rats. Methysergide and cinanserin stimulated behaviour in non-receptive rats. All the drugs which increased 5HTP activity, i.e., 5HTP, zimelidine, alaproclate, WY 26002 and quipazine stimulated sex behaviour in non-receptive rats. In rats that had been ovariectomised only, part of this effect was probably due to stimulation of adrenal progesterone, but a significant stimulatory effect could still be observed in ovariectomised-adrenalectomised rats. 5HT also had a significant inhibitory effect on receptive rats, and the other agonists showed a similar but non-significant tendency. In view of the fact that 4 out of 5 of the 5HT antagonists inhibited sexual behaviour, we hypothesise that 5HT has a stimulatory role in the control of female sexual behaviour. The possible mechanisms mediating the dual action of 5HTP on female sexual behaviour are discussed.

5-Hydroxytryptophan↗

Peripubertal changes in the nature of LH.

Administration of pregnant mare serum gonadotrophin (PMSG) to peripubertal rats, aged 27 days, induces ovulation provided the animals weigh more than 60 g at the time of the injection. In an attempt to determine whether the apparent immaturity of the ovaries in smaller rats is associated with an inability of the pituitary gland to secrete LH, the biological and immunological properties of LH in peripubertal PMSG-treated rats were examined. A single injection of PMSG caused a marked hypersecretion of LH in rats aged 27 days. The LH in the plasma of rats weighing more than 60 g was active in both the radioimmunoassay and the cytochemical bioassay but that in smaller rats was active only in the former. Plasma from both groups of rats stimulated the release of testosterone from dispersed Leydig cells. Luteinizing hormone-releasing hormone stimulated the secretion, in vitro, of immunoreactive, cytochemically active LH by pituitary tissue from rats weighing over 60 g. The LH released in vitro from tissue from the smaller animals, like that in their plasma, was active in the radioimmunoassay but not in the cytochemical system. The results suggest that an abrupt change in the nature of LH occurs at puberty and that ovulatory cycles commence only when the pituitary gland secretes the adult form of LH with a full spectrum of biological activity.

Animals↗

Influence of growth hormone, corticosterone, corticotrophin and changes in the environmental temperature on pituitary-ovarian function in the immature rat.

The influence of various endocrine and environmental factors on pituitary-ovarian function was studied in peripubertal rats treated with pregnant mare serum gonadotrophin (PMSG). Pregnant mare serum gonadotrophin induced ovulation in rats aged 27 days provided they weighed over 60 g. The response was preceded by a marked hypersecretion of LH which was detectable by radioimmunological and biological assay methods. In contrast, smaller rats of the same age did not ovulate in response to PMSG apparently because of the secretion of a pleiomorphic form of LH which, although immunoreactive, appeared to be biologically inactive. Ovarian function, assessed by response to exogenous gonadotrophins and by measurement of 125I-labelled human chorionic gonadotrophin binding, was normal despite the presence of the biologically inactive pleiomorph. Exposure of the small PMSG-treated rats to a high environmental temperature (39 degrees C) or treatment with corticosterone or GH altered the nature of the LH in the blood so that it was active in both assay systems and facilitated ovulation as also did ACTH. The results suggest that the abrupt change in the nature of the LH released by the pituitary gland essential for the initiation of ovulation may be affected by GH, corticosterone or a raised environmental temperature.

Adrenocorticotropic Hormone↗

Evidence for a stimulatory beta-adrenergic component in the release of the ovulatory LH surge in pro-oestrous rats.

The effect on ovulation of intraventricular infusions of noradrenaline, adrenaline and various pharmacological agents acting on the adrenergic receptor subtypes were investigated in cyclic female rats on the day of pro-oestrus. The inhibitory effects on ovulation of the different infusions were monitored by administering the drugs before 11.00 h (several hours before the critical period for the ovulatory LH surge). In experiments designed to show how the drugs under investigation might stimulate ovulation, pentobarbitone sodium (35 mg/kg) was given at 14.30 h; this anaesthetic inhibits ovulation and its effects can be overcome by substances that advance the preovulatory LH surge. Noradrenaline (an alpha-agonist) stimulated ovulation when administered on the morning of pro-oestrus to rats injected with pentobarbitone early in the afternoon of the same day. Phenoxybenzamine and phentolamine (non-selective alpha-antagonists) and clonidine (a selective alpha 2-agonist) all inhibited ovulation when infused on the morning of pro-oestrus. Yohimbine (a moderately selective alpha 2-antagonist) neither stimulated nor inhibited ovulation. Both isoprenaline (a non-selective beta-agonist) and fenoterol (a selective beta 2-agonist) stimulated ovulation in pentobarbitone-treated rats when administered on the morning of pro-oestrus and fenoterol was also able to overcome the pentobarbitone block when infused later in the afternoon. Propranolol (a non-selective beta-antagonist) and metoprolol (a selective beta 1-antagonist) were stimulatory only when administered in the afternoon. Adrenaline (both an alpha- and beta-agonist), prenalterol (a selective beta 1-agonist), atenolol (a selective beta 1-antagonist) and ICI 118,551 (a selective beta 2-antagonist) neither stimulated nor inhibited ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗