Control of the hypothalamus-pituitary-adrenal axis in young and older rats injected with thyroxine1–3

Summary Administration of T₄ on alternate weeks for 30 weeks at a dosage which does not alter body weight depresses basal serum corticosterone levels in older rats (575 days), but not in young animals (260 days). Similar serum corticosterone response to HPA axis stimulation occurs regardless of age or T₄ injection.Presented in part at the 8th Annual National Meeting of the American Aging Association, October 1978, San Francisco.Supported by an FRC grant, Graduate College, Bowling Green State University.Acknowledgment is made of the technical assistance of L. Carter, P. Froelich, R. Froelich, J. Ku, M. Meserve and D. Schulte.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Effects of handling normal and bulbectomized rats at adrenal and plasma corticosterone levels

Summary Normal and bulbectomized adult rats, male and female, handled daily for 4 weeks, show plasma and adrenal corticosterone values significantly lower than the non-handled ones.     

Effect of lesions of the locus coeruleus complex on the circadian rhythm of plasma corticosterone in the mouse.

An apparently transient elevation of basal morning (08.00 h) plasma corticosterone levels in male mice was found 48 h after bilateral electrolytic lesions of the brainstem locus coeruleus complex but was not observed 6 weeks after lesioning.     

Effect of lesions of the locus coeruleus complex on the circadian rhythm of plasma corticosterone in the mouse

Summary An apparently transient elevation of basal morning (08.00 h) plasma corticosterone levels in male mice was found 48 h after bilateral electrolytic lesions of the brainstem locus coeruleus complex but was not observed 6 weeks after lesioning.Supported by Alfred P. Sloan Foundation research fellowships awarded to W.G. Luttge and S.F. Zornetzer.     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

Summary 24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Inhibition of TSH-stimulated thyroid hormone release and potentiation of TRH-stimulated TSH release by indomethacin in perifusion systems of rat thyroids and pituitaries

Using indomethacin (Ind), a prostaglandin synthesis inhibitor, in vivo experiments in rats and in vitro experiments with perifusion systems of rat thyroids and pituitaries were conducted. After 35 days of intragastric infusion of Ind, serum TSH levels were markedly increased, the thyroid was swollen and, as a consequence, T3 and T4 levels were normal. The T3 release from perifused rat thyroids under continuous stimulation with 10 mU/ml TSH was inhibited significantly (p less than 0.01) by 1.0 X 10(-6) M Ind. On the other hand, the TSH release from perifused rat pituitaries under TRH stimulation was enhanced conspicuously by Ind. It was concluded that Ind decelerated thyroid hormone release from the thyroid and accelerated TSH release from the pituitary in perifusion systems.     

Circadian rhythm of plasma corticosterone in vagotomized rats

Summary In vagotomized rats, 2 weeks after surgery, the amplitude of the circadian rhythm of plasma corticosterone was extremely low, indicating that gastrointestinal activity may be in part involved in the hypothalamo-hypophyseal circadian rhythmicity.     

Corticoadrenal and behavioral response to open field in pairs of male rats either familiar or non-familiar to each other

The effect of the presence either of a familiar or non-familiar conspecific animal on serum corticosterone and some behavioral responses in the open field was studied in male Sprague-Dawley rats. Animals tested in presence of a familiar animal showed a higher corticosterone response and a higher defecation rate. It suggests that rats experienced more emotional reactivity in presence of a familiar animal than in presence of a non-familiar one. Time spent in social interaction was higher in non-familiar pairs; however, ambulation and rearing were lower, suggesting competition between social investigation and novel environment exploration.     

The effect of eating behavior on the circadian rhythm of plasma corticosterone in growing rats]

The circadian rhythm of plasma corticosterone was studied in growing Rats fed on an ad libitum or controlled feeding schedule (six meals per day). Circadian plasma corticosterone rhythm was conventional in ad libitum Rats. Increases of circulating hormone occurred during the last light hours and the first dark hours. Plasma corticosterone rhythm was modified by controlled feeding. Meal feeders exhibited a high value during the last light hours and a secondary hump at midnight. Feeding schedule was not the main synchronizing factor in rat circadian corticosterone rhythm.     

The role of sex steroid in two avian song behaviours differing in ontogenetic process

The male Bengalese finch,Lonchura striata, has two types of song behaviour (directed song, DS and undirected song, US). DS and US share a basically identical syllable repertoire, sequence pattern and tempo, but differ in the time course of appearance during the maturational process. In order to examine whether this results from a difference in testosterone (T) dependency, we studied developmental changes in the fecal T level and the amounts of DS and US during the 2–4 month period (N=7). DS appeared between 83 and 94 days of age, 4–16 days after a rise in the fecal T level. In contrast, US appeared earlier and at high frequency even when T was still at a very low level. These results suggest that DS is more dependent on the T level than US, and is not activated until the T level rises during the maturational process.     

Effects of thyroxine and exercise on the glandular and plasma levels of corticosterone in the male rat

Summary The results presented here demonstrates that the thyroid gland is essential for normal corticosterone production. They further show that exercise stimulates this production whether the thyroid gland is present or not. The release or metabolism of corticosterone seems dependent upon an intact thyroid gland since plasma levels of corticosterone are decreased during exercise if the thyroid is absent. The administration of thyroxine is not sufficient to renew these levels.     

Variations of testosterone uptake by gonadotropic cells of the adenohypophysis of the rat

Testosterone (T) could be detected by immunocytochemistry after cryoultramicrotomy and T is likely bound on a binding site of a high affinity. Castration and adrenalectomy involve a swift disappearance of T in the gonadotropic cells. Synthesis of new binding sites was induced by daily T injection in the castrated and surrenalectomized Rat from 90 days. This synthesis is inhibited by cycloheximide. These data suggest that binding sites are proteins. The captation of T by the gonadotropic cells was diminished similarly at the diminution of T, afterwards, T captation was stabilized at a weak level which became stable for several weeks. It seems that immunocytochemistry permits the study of the variation of T captation by Rat pituitary gonadotropic cells.     

Parenteral feeding abolishes the circadian adrenocortical rhythm in rats

Summary The circadian rhythm of the blood corticosterone level disappeared in rats that had been given a liquid diet i.v. during a resticted time of day for 10 days, suggesting an important role of the oro-gastrointestinal tract in formation of the rhythm.     

Corticotropin releasing factor increases the adrenocortical responsiveness to adrenocorticotropin

Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 g compared with 5 g per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p<0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.Acknowledgments. This research was supported by grant MT-5183 from the Medical Research Council of Canada and by the Department of Medicine, University of Kentucky.     

Effect of glucocorticoids injected into pregnant female mice and rats on weight of male sexual glands in adult offspring and testosterone level in fetus in genotype-dependent

Injection of corticosterone into CBA/Lac, C57BL/6J and BALB/c mice, or hydrocortisone into aggressive and domesticated rats, on days 16 and 18 of pregnancy decreased the weight of sexual glands in adult male offspring of the C57BL/6J and domesticated mothers but increased these values in male offspring of the CBA/Lac and aggressive mothers. When injected into pregnant aggressive and domesticated rats, corticosterone affected testosterone levels in 21-day-old male fetuses. The changes were also genotype-dependent and followed the course of changes in the weight of the accessory sex glands in adults. It is suggested that glucocorticoids given during the prenatal period can effect plasma testosterone levels of male fetuses and the development of the sexual glands in a genotype-dependent manner.     

Luteolytic action of LHRH in women]

Several subcutaneous administrations of 250 microgram of LHRH (4 or 5 adminstrations at 4-hourly intervals per day) between the 2nd and 7th day post-ovulation in 4 normal women led to early luteolysis as demonstrated by a fall in serum progesterone concentration and early onset (2 to 3 days earlier) of menstruation.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.