Short history of neuroendocrinology and the International Society of Neuroendocrinology.
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History, 20th Century↗
Biomedical subjects
J Meites
Publications and source records attributed to J Meites.
Remembrance: neuroendocrinology and aging. A perspective.
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Aging↗
A comparison between hormone levels and T lymphocyte function in young and old rats.
There is growing evidence that changes in hormone secretion during aging can alter some functions of the thymus. In order to identify further relationships between changes in endocrine and thymic function during aging we measured the circulating levels of prolactin (PRL), growth hormone (GH) thyrotropin (TSH) thyroxine (T4) and triiodothyronine (T3), and determined their relation to a number of T lymphocyte functional indices in 20 young (4 months) and 20 old (28-30 months) Long-Evans male rats. Half of the young and old rats were chronically cannulated in order to obtain sequential plasma samples for measuring PRL, GH and TSH by RIA. Total T4 and T3 were measured by RIA in the trunk serum of all animals. Thymus and spleen cell cultures from each rat were established and used to assess the ability of thymocytes to respond to mitogens and lymphokines as well as to measure the levels of IL-2 production by splenic lymphocytes. Mean plasma GH and serum T4 were significantly lower in old as compared to young rats (P less than 0.05 and P less than 0.001 for GH and T4, respectively), while PRL, TSH and T3 did not show significant age changes. Thymic cell number showed a 100-fold decrease in old as compared to young animals (10.6 +/- 3.0) x 10(6) vs. (898 +/- 98) x 10(6) cells, respectively) whereas no age change was detected in spleen cell numbers. The proliferative response of thymocytes exposed to Con A, IL-1, Con A + IL-1 or Con A + IL-2, was consistently higher in young than in old animals while the capacity of splenocytes to release IL-2 in response to Con A was not statistically different in young and old rats. The age changes in serum T4 showed a significant correlation with those in thymocyte count as well as with those in IL-1 + Con A- and IL-2 + Con A-induced thymocyte proliferation. Plasma GH showed a significant inverse correlation with splenocyte IL-2 release. Our results suggest, although do not prove, that the lower T4 and GH secretion that typically develops in old rats may play a causal role in some of the changes that occur in thymic-dependent functions during aging.
Aging↗
Differential effect of aging on serum levels of prolactin and alpha-melanotropin in rats.
Prolactin (PRL) and alpha-melanocyte-stimulating hormone (alpha-MSH) are the only two pituitary hormones whose basal secretion is under tonic dopaminergic inhibition exerted by the hypothalamus. In the female rat, continuous exposure to estrogens is believed to depress hypothalamic dopaminergic activity and lead to the appearance of PRL-secreting pituitary adenomas during aging. Since there is no information about the impact of aging on circulating alpha-MSH levels, it was of interest to assess and compare the serum levels of PRL and alpha-MSH in male and female rats of different ages. Young (3-4 months) and old (24-25 months) male and female Sprague-Dawley rats as well as senescent (33-35 months) females were killed by decapitation between 10 AM and 1 PM, and pituitaries were immediately removed and dissected. Hormones were measured in unextracted trunk serum by radioimmunoassay. Serum PRL levels were (mean +/- SE), 18.4 +/- 2.0, 26.8 +/- 3.8, 19.8 +/- 2.5, 43.0 +/- 7.5, and 193.5 +/- 47.6 ng/ml for young and old males, and young, old, and senescent females, respectively. Serum alpha-MSH levels were 243.2 +/- 15.2, 252.9 +/- 24.8, 320.0 +/- 31.3, 234.7 +/- 19.1, and 374.0 +/- 29.7 pg/ml for young and old males, and young, old and senescent females, respectively. Anterior pituitary and neurointermediate lobe weights increased significantly with age in both sexes, although the change was particularly conspicuous in the females. We conclude that aging does not have a major impact on circulating alpha-MSH levels in rats and that melanotrophs probably have a greater ability than prolactotrophs to withstand age-associated alterations in central regulatory mechanisms.
Aging↗
Role of hypothalamic catecholamines in aging processes.
Defects that develop in the hypothalamic area of the brain are believed to initiate many declines in body functions in aging rats and mice. The decreases found in hypothalamic norepinephrine and dopamine are particularly important since they lead to reduced gonadotropic hormone secretin and cessation of estrous cycles in female rats and a decrease in testosterone secretion in male rats, lower GH and somatomedin (IGF-I) secretion and reduced protein synthesis, diminished thyroid hormone secretion and lower body metabolism, higher PRL secretion and development of numerous mammary and pituitary tumours, and reduced immune competence. The reduction in hypothalamic norepinephrine and dopamine activity is believed to be due to damage and loss of neurons owing to toxic products formed during metabolism of norepinephrine and dopamine; to the damaging effects to neurons produced by the chronic action of estrogen, PRL, and indirectly by adrenal glucocorticoids; and to changes in enzymes responsible for synthesis and metabolism of norepinephrine and dopamine. When old rats are given drugs that elevate norepinephrine and dopamine, most of the above and other decrements of aging are delayed or reversed, and length of lifespan may be prolonged. Decreases in hypothalamic norepinephrine and dopamine have also been reported in elderly human subjects, but it is unknown whether these are related to declines in body functions.
Aging↗
Gonadal function in aging rats and its relation to pituitary and mammary pathology.
In the female rat, aging is characterized by a high incidence of prolactin (Prl)-secreting pituitary adenomas and mammary tumors. In contrast to this, old males show only a moderate to low incidence of pituitary and mammary pathology. Since gonadal steroids and Prl are thought to be key factors in the genesis of the above neoplastic pathologies, it was of interest to compare the serum levels of progesterone (P), estradiol (E2), testosterone (T) and Prl with the incidence of pituitary and mammary tumors in aging male and female rats. Young (3-4-month; YF), old (25-month; OF) and senescent (33-35-month; SF) female and young (3-4-month; YM) and old (24-26-month; OM) male Sprague-Dawley rats were killed by decapitation and their pituitaries weighed. Serum sex steroids and Prl were measured by RIA. The average life span of females but not males was markedly extended by systematic removal of mammary tumors. Females showed a rising incidence of mammary tumors after 14 months of age. In males, this pathology which began to appear at 16 months, had a much lower incidence than in females at all ages. Serum levels of E2 were (means +/- S.E.M.) 22.0 +/- 1.6; 18.9 +/- 0.8; 32.9 +/- 2.5; 37.3 +/- 2.0 and 32.2 +/- 3.0 pg/ml for YM, OM, YF, OF and SF, respectively. Serum P was 1.4 +/- 0.3; 1.6 +/- 0.2; 10.4 +/- 2.2; 9.7 +/- 3.3 and 6.8 +/- 0.8 ng/ml for YM, OM, YF, OF and SF, respectively. Serum T was 1578.9 +/- 188.7; 807.6 +/- 103.0; 197.5 +/- 11.8; 223.7 +/- 25.5 and 176.9 +/- 20.7 pg/ml for YM, OM, YF, OF and SF, respectively. Finally, serum Prl was 14.9 +/- 1.7; 21.9 +/- 4.0; 15.9 +/- 1.4; 52.4 +/- 9.4 and 170.8 +/- 31.1 ng/ml for YM, OM, YF, OF and SF, respectively. A strong correlation was found between serum Prl and anterior pituitary weight in OM, OF and SF, but not between serum Prl and sex steroid levels or sex steroid ratios. We conclude that, although the sex-related differences in mammary and pituitary tumor incidence during aging in rats can be partially accounted for by the different serum profiles of Prl and gonadal steroids in each sex, sex-associated differences in target tissue susceptibility should also be considered as an important determinant of the level of tumor incidence.
Aging↗
Effects of underfeeding and refeeding on GH and thyroid hormone secretion in young, middle-aged, and old rats.
The effects of a 50% reduction in normal food intake for a period of 10 weeks were measured on secretion of growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) in 5 1/2-6 1/2-month old, 13 1/2-month-old, and 17 1/2-18 1/2-month-old male rats. In full-fed controls, GH, T3, and T4 were lower in the old and middle-aged than in the young rats. By the 10th week of underfeeding, GH, T3, and T4 were reduced in all age groups, but the decrease in T3 and T4 in the middle-aged and old rats was greater than in the young rats. Pulses of GH ceased in all the underfed groups. Upon refeeding for 5 days, pulses of GH and levels of GH returned to full-fed control values in the young and middle-aged but not in the old rats. T3 values in the young and middle-aged rats returned to full-fed control levels, but remained below control levels in the old rats. T4 values reached control levels in all age groups upon refeeding. The differences in the response to underfeeding and refeeding by the middle-aged and old rats as compared to the young rats may be due to their initially lower secretion of GH and thyroid hormones and to the age-related decrease in neuroendocrine function.
Aging↗
Changes in circulating levels of neuroendocrine and thymic hormones during aging in rats: a correlation study.
It is well established that during early life the thymus gland and the neuroendocrine system influence each other's maturation. Furthermore, there is a growing body of evidence indicating that the immune and neuroendocrine systems also function as a bidirectional network during adult life. In order to assess possible changes in the thymic-neuroendocrine network during aging, we undertook to measure and correlate the circulating levels of several neuroendocrine and thymic hormones in young (3 month) and old (26 month) male Sprague-Dawley rats. Sequential plasma samples were obtained from chronically cannulated, nonstressed animals every 30 min for 5 h. Two days later rats were killed between 11:30 a.m. and 1:30 p.m. and trunk serum was obtained. All hormones were measured by radioimmunoassay. Growth hormone (GH), prolactin (PRL), thyrotropin (TSH) and corticosterone were measured in plasma, whereas thyroxine (T4), triiodothyronine (T3), thymosin alpha 1 (T alpha 1) and thymosin beta 4 (T beta 4) were determined in trunk serum. The circulating levels of T3, PRL, corticosterone and T beta 4 did not show significant differences between young and old rats, whereas GH, T4, T alpha 1, and thymus weight showed a significant age-related reduction. The anterior pituitary (AP) weight and plasma TSH were significantly higher in old than in young rats. Three pairs of parameters showed highly significant levels of linear correlation: AP weight vs. T alpha 1; thymus weight vs. T4 and T alpha 1 vs. T4 (p less than 0.01, p less than 0.001 and p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Homeostatic thymus hormone stimulates corticosterone secretion in a dose- and age-dependent manner in rats.
There is increasing evidence that the neuroendocrine system is responsive to hormonal signals generated by the immune systems. In particular, interleukin-1 and thymosin have been shown to stimulate the pituitary-adrenal axis in young animals. We report here that homeostatic thymus hormone (HTH), a well-characterized thymic preparation, increases plasma levels of corticosterone but not prolactin (PRL) in a dose- and age-dependent manner in male Sprague-Dawley rats. Young (3 months) and old (26 months) conscious, free-moving animals carrying an indwelling atrial cannula received the substances to be tested via the cannulas. Plasma samples were taken every 30 min for 5 h and hormones were measured by radioimmunoassay. HTH doses of 1 and 8 mg/kg body weight injected into young rats elicited a 7.8- and 12.8-fold increase in plasma corticosterone, respectively, as compared to saline-injected controls. The HTH-induced peak corticosterone levels were reached within 1.5 and 2.5 h after HTH injection. Plasma PRL was not affected by HTH in either age group. A single dose of 8 mg HTH/kg body weight induced a smaller corticosterone response in old than in young rats, although the time course of the response was similar in both age groups. The present results further suggest the existence of a lymphoid-neuroendocrine axis in young animals. The data also suggest that a disruption in immune-endocrine integration occurs during aging in rats.
Aging↗
Aging: hypothalamic catecholamines, neuroendocrine-immune interactions, and dietary restriction.
The decline in hypothalamic catecholamine (CA) activity with age in rats leads to a reduction in hormone secretion by the neuroendocrine system, and results in decreased reproductive function, a reduction in protein synthesis, development of numerous mammary and pituitary tumors, and probably contributes to the decline in immune function. Some of these same effects can be produced in young rats by administration of drugs that lower hypothalamic CA activity. Administration of drugs to old rats that elevate hypothalamic CA activity can inhibit or reverse the reproductive decline, increase protein synthesis, induce regression of mammary and pituitary tumors, decrease disease incidence, probably elevate immune function, and significantly extend the life span. Therefore, hypothalamic CA have a critical role in the development of aging processes. When young or mature rats or mice are fed a caloric restricted diet, aging processes are inhibited and life span is significantly lengthened. These effects are believed to be mediated primarily via the neuroendocrine system, since calorie restriction results in decreased secretion of hypothalamic, pituitary, and target gland hormones. The decline in hormone secretion leads to a reduction in most body functions, lowers whole body metabolism, and reduces gene expression, and thereby results in a decreased rate of aging of body tissues and longer life. These effects of caloric restriction can be counteracted by administration of hormones, providing evidence that the favorable effects on aging are mediated by reducing hormone secretion.
Aging↗
Differential effect of homeostatic thymus hormone on plasma thyrotropin and growth hormone in young and old rats.
There is increasing evidence that the neuroendocrine system is responsive to hormonal signals generated by the immune system. Thus, interleukin-1, hepatocyte stimulating factor and thymosin have been shown to stimulate adrenocorticotropin, beta-endorphin and luteinizing hormone secretion. We report here that homeostatic thymus hormone (HTH), a well-characterized thymic preparation, reduces plasma thyrotropin (TSH) and growth hormone (GH) in young (3 months) Sprague-Dawley male rats, but fails to do so (TSH) or has a significantly weaker effect (GH) in old (26 months) animals. Young and old conscious, free-moving rats carrying an indwelling atrial cannula received the substances to be tested via the cannulas. Plasma samples were taken every 30 min for 5 h and hormones were measured by RIA. In the young rats, HTH (8 mg/kg body wt) induced a marked reduction in plasma TSH which was significantly greater than the normal circadian decline observed in saline-injected young controls. The old rats displayed high basal levels of TSH which showed no circadian rhythmicity and did not respond to HTH. Plasma thyroxine (T4) showed a significant age-related reduction but was not affected by HTH. The above dose of HTH significantly reduced plasma GH in young and old rats, but the effect was greater in the young animals. Mean basal levels of plasma GH were significantly lower in old than in young rats. The present results suggest that HTH, whose production by the thymus is known to be stimulated by TSH and GH, is involved in an inhibitory feedback loop regulating plasma TSH and GH in young rats. Our data also suggest an age-related desensitization of the TSH and GH systems to thymic influence in this species.
Aging↗
Aging and anti-aging effects of hormones.
Hormones can promote or inhibit aging depending on the experimental conditions employed. The aging effects of hormones are demonstrated by reducing hormone secretion by hypophysectomy or chronic underfeeding in young or mature rats. These result in depressing whole body metabolism, growth, body temperature and blood glucose levels, heart rate and vital capacity, gene expression, etc., but delaying aging of tissues, suppressing development of pathology and tumors, and, in underfed rats, prolonging life span. The anti-aging effects of hormones are demonstrated by elevating hormone levels in old rats whose hormones have declined as a result of dysfunctions that develop in the neuroendocrine system with age. An increase of hormones in these rats promotes gene expression, elevates protein synthesis, and enhances metabolism, growth, and function of stimulated organs and tissues.
Adrenal Cortex Hormones↗
Episodic growth hormone secretory pattern in male rats: relationship to gonadal steroid hormones.
In the present study sequential blood samples were obtained from freely-behaving male rats bearing chronic intracardial venous cannulae. Blood samples were obtained at 20 min intervals for 6 h from intact rats, castrated rats, castrated rats treated with either testosterone propionate (TP) or estradiol benzoate (EB) and intact rats treated with either TP or EB. Intact rats demonstrated normal episodic GH secretion. The mean baseline GH concentration was similar in intact and castrated rats, while the overall mean plasma GH levels and the magnitude of the mean plasma GH secretory spikes were significantly higher in intact rats. Injection of castrated rats with TP completely counteracted the effect of castration on GH secretory pattern. Injection of TP to intact male rats did not induce any significant changes in the GH secretory pattern. Treatment of intact males with EB significantly elevated mean baseline GH concentration, while the magnitude of the mean GH secretory spikes was significantly reduced. When EB was injected to castrated males, the overall mean GH levels and the magnitude of the mean GH secretory spikes were significantly reduced, while the mean baseline GH was significantly elevated. The data of the present work suggest that gonadal steroids are responsible, at least in part, for the differences in GH secretory pattern between males and females; and that the increase in the magnitude of GH secretory spikes in males could account for the greater increase in growth rate at puberty in males than in females.
Animals↗
Evidence that underfeeding acts via the neuroendocrine system to influence aging processes.
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Aging↗
Neuroendocrine biomarkers of aging in the rat.
The genome and environmental agents are believed to regulate aging processes mainly via the homeostatic and integrative mechanisms of the body, which consist primarily of the neuroendocrine, immune and cell-to-cell communicating systems. Of these, the neuroendocrine system is considered to be the most important since it regulates to a greater or lesser degree all body functions, in old age as well as in early and mature life. We have studied mainly three aging events in the rat: the reproductive decline, development of numerous mammary and pituitary tumors and the decrease in GH secretion and protein synthesis. We have found that all three are caused primarily by faults that develop in hypothalamic function, particularly the decline in norepinephrine (NE) and dopamine (DA) activity. This decline appears to be caused largely by damage to hypothalamic neurons as a result of the chronic action of hormones, toxins, free radicals, cross linkages, lipofuscin accumulation and "wear and tear". Administration of drugs that increase hypothalamic NE and DA activity can delay or reverse all three aging events. Changes in hormone secretion, estrous cycles, tumor development and protein synthesis can be measured and used as "biomarkers of aging" in the rat.
Aging↗
Importance of the neuroendocrine system in aging processes.
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Aging↗
Increased secretion of somatostatin-28 from hypothalamic neurons of aged rats in vitro.
The purpose of this experiment was to determine whether increased secretion of somatostatin or alterations in its molecular form contribute to the age-related decline in growth hormone secretion. Median eminences were removed from male Sprague-Dawley rats (3-4 and 21-24 months of age) and superfused with Krebs-Ringer bicarbonate buffer with 0.5 mg/ml bacitracin. After 40 min, tissues were stimulated with 55 mM K+ for 5 min and fractions collected for 60 min. Tissue and superfusate were analyzed for somatostatin using a highly specific antiserum which cross-reacts with somatostatin-14 and -28. Somatostatin release was expressed as a fractional efflux of somatostatin tissue content. In young rats, somatostatin increased from basal levels of 22 +/- 5 X 10(-4) to 57 +/- 3 X 10(-4) in response to 55 mM K+ and returned to basal levels. Old rats exhibited similar basal levels of somatostatin efflux (25 +/- 5 X 10(-4)) but increased to 91 +/- 19 X 10(-4) in response to K+. This represents an 89% greater increase in somatostatin fractional efflux in old as compared to young rats (P less than 0.05). The molecular form of somatostatin released during K+ stimulation was determined by fractionating samples on Sephadex G-25. In young animals, both somatostatin-14 (31% of total immunoreactivity) and somatostatin-28 (69% of total immunoreactivity) were released by hypothalamic neurons. In old rats, similar absolute levels of somatostatin were released in response to K+ but greater quantities of somatostatin-28 (87% of total immunoreactivity) were secreted.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗