Changes In Endocrine Function Research Articles

Influence of Age on Neurotransmitter Function

Regulation by neurotransmitters of anterior pituitary hormone secretion is complex and a thorough understanding of their normal role in hormone secretion is a prerequisite to understanding their involvement in age-related changes in endocrine function. To date, uncertainties far out-number demonstrated causative relationships between alterations in neurotransmitter release and resulting age-associated changes in hormone secretion. The best demonstrated relationships are the following. First, a decline in function of the TIDA system is responsible, in part, for the age-related elevation in prolactin secretion and may be involved in the decline in LH secretion. Second, the age-related decrease in hypothalamic norepinephrine turnover plays a role in the decline in LH and GH secretion and may be involved in alterations in TSH secretion during aging. Third, the decline in circadian activity of suprachiasmatic nucleus serotoninergic neurons may account for the blunting of circadian rhythms in the secretions of several anterior pituitary hormones in old animals. Fourth, evidence exists for an age-related decline in function of LHRH neurons, which may contribute to the observation of blunted LH secretion in old animals. Finally, somatostatin release may be increased in old animals, which likely contributes to the age-related decline in GH secretion. Other hypothalamic-releasing hormones have only recently been isolated and characterized; thus, little research on their age-related alterations has been done. Research on these neuropeptides will contribute further to our understanding of the role of neurotransmitters in age-related alterations in hormone secretion.

Endocrine function changes in young males during long-term antiepileptic therapy with phenobarbitone and carbamazepine.

The effects of long-term antiepileptic combined therapy with phenobarbitone (PB) and carbamazepine (CBZ) on the major endocrine functions were evaluated in a selected group of 15 young males with partial epilepsy. The plasma basal levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyrotropin (TSH), cortisol (CO), dehydroepiandrosterone-sulfate (DHEA-S), adrenocorticotropin (ACTH), growth hormone (GH), prolactin (PRL) and testosterone (T) were determined. TSH and PRL were also assessed in response to i.v. injection of thyrotropin releasing hormone (TRH). The results were compared with those found in 37 age-matched male volunteers. The most remarkable changes affected pituitary-thyroid axis and pituitary-adrenal axis, while the hypothalamic-pituitary response was normal. No correlation between hormonal changes and duration of epilepsy and therapy or ADs plasma levels was found. There seems to be considerable individual variability of response to antiepileptic therapy, probably depending on peripheral changes in the hormonal metabolism.

Changes in adrenal and testicular activity monitored by salivary sampling in males throughout marathon runs.

Measurement of cortisol and testosterone in saliva samples provided by marathon runners at 6.4 km (4-mile) intervals has been used for monitoring acute changes in adrenal and testicular activity, and the changes compared with mean values in timed samples on five rest days. The collection of mixed whole saliva was well accepted; the missed sample rate in the 8 runners in the Cardiff marathon was less than 10%. On rest days, salivary cortisol and testosterone were within the normal male range and showed a circadian rhythm; mean values at 08.00 h (23.5 nmol L-1; 258 pmol L-1, p less than 0.001, p less than 0.001 respectively) were higher than at 22.00 h (2.8 nmol L-1; 130 pmol L-1). In samples collected at 09.00 h, immediately prior to the Cardiff marathon, cortisol (25.1 nmol L-1) and testosterone (304 pmol L-1) were higher than the mean values (14.9 nmol L-1; 209 pmol L-1) on non-run days. Concentrations of both steroids increased during the marathon; testosterone peaked (442 pmol L-1) at 21 miles, whereas cortisol continued to increase, being maximal (87.9 nmol L-1) at 30 min after completion of the run. Four of the runners in the Cardiff marathon also participated in the Bristol marathon and the changing patterns in salivary hormones were strictly comparable. Salivary sampling would appear to be of value in monitoring acute and rhythmic changes in endocrine function in marathon runners. The temporal relationship between changes in salivary cortisol and testosterone are consistent with direct inhibition of testicular secretion by high cortisol concentrations.

Lead, age and aggression in male mice

The impact of eleven weeks of ingestion of a 0.5% lead acetate solution on agonistic behavior of male Binghamton Heterogeneous stock mice (either 120 or 660 days of age) was examined. Similar aged mice were paired for aggression testing. Not surprisingly, younger mice, regardless of fluid history fought more vigorously than older mice. However, when mice of similar fluid history were paired together, lead ingestion decreased the latency to fight only in older mice. Regardless of their prior fighting history, when lead treated mice fought similar aged controls, the lead exposed mice in younger pairs were typically subordinate; but in older pairs, lead exposed mice were dominant. These results, coupled with extant literature concerning age-related changes in endocrine function, pituitary-adrenal activity, and lead-induced changes in hippocampal function suggest that future work directed at mechanism(s) underlying lead-induced alterations in agonistic behavior should consider life span changes in biobehavioral profiles.

Hormones and age

AbstractEndocrine disorders may present in an atypical way in old people and are often mistaken for ageing itself. Ageing produces a variety of changes in endocrine function, most of which are minor and of little clinical relevance in contrast to the significant morbidity and mortality associated with endocrine disease in the elderly. Nearly all systems may be affected in the elderly and the possibility of underlying hormonal dysfunction should not be overlooked, because of the opportunities for curative treatment. In most instances the investigations employed to diagnose endocrine disorders in the elderly are similar to those used in younger patients. However, ageing and multiple pathology have an important effect upon the biochemical effects of both thyroid disease and diabetes and so these are considered in more detail.

Variable adrenocortical function in acute medical illness.

Acute medical illness may produce dramatic changes in endocrine function. Although cortisol levels rise in acute medical illness, changes in adrenocortical function and reserve have not been well documented in medical ICU patients. We evaluated plasma ACTH and cortisol levels, and cortisol response to intravenous ACTH in 40 acutely ill patients and 20 anxious but nonacutely ill controls. A wide range of plasma cortisol values (212 to 8430 nmol/L) was observed. More severely ill patients did not necessarily have higher plasma cortisol values. Patients who survived hospitalization had lower mean initial and post-ACTH cortisol levels than patients who succumbed. ACTH levels varied widely and correlated poorly with levels of plasma cortisol. There was no evidence of occult adrenocortical insufficiency. We conclude that plasma cortisol elevations are common in acute medical illness.

Differential effects of viral infection on islet and pituitary cell lines.

Although reovirus infection may lead to changes in endocrine function in vivo, little is known about the precise interaction of reovirus with endocrine cells. In this study we have examined the effects of reovirus infection on two types of endocrine cells, GH4C1 cells and RINm5F cells. Both type 1 reovirus and type 3 reovirus infect the two cells lines and appear to grow equally well. Viral replication occurred within the first 24 h following infection after which viral titers remained stable for 3 days. By 48-72 h after viral infection, substantial cytopathic effects were noted in RINm5F cells infected with both type 1 and type 3 reovirus. In GH4C1 cells, type 3 reovirus was most effective in producing cell death, and type 1 reovirus was significantly less cytotoxic despite a similar viral titer. Only type 1 reovirus caused a specific inhibition of overall protein and DNA synthesis, and this occurred only in the RINm5F cells. Over the time course studied, GH4C1 cells successfully infected with type 1 reovirus demonstrated no cytopathic effects, and only minimal alterations in cellular function were noted. Intracellular insulin content and insulin secretion, a "luxury function" of the RINm5F cells, were also surprisingly well maintained in the first 48 h after viral infection. In addition, virally infected cells were able to respond to glyceraldehyde, an insulin secretagogue, although the response appeared to be somewhat blunted compared to that of control cells. These results suggest that viral infection of endocrine cells results in specific alterations that depend on the nature of the infecting virus. In addition, the cellular environment of the host cell may be an important determinant in the outcome of viral infection.

Effects of antihypertensive drugs on endocrine function.

Pharmacological treatment of hypertension can cause clinically significant alterations in endocrine function through effects on glucose homeostasis, thyroid and parathyroid hormones, adrenal steroid metabolism and reproductive/pituitary physiology. Long term use of thiazide diuretics causes deterioration in glucose tolerance, probably secondary to potassium depletion. Hypoglycaemic complications of beta-blockers (mainly the non-selective compounds) can be dramatic, especially in type I diabetics. Clonidine, diazoxide and calcium antagonists have all been associated with deterioration in glucose tolerance and their long term use should be avoided in type II diabetics if possible. Propranolol lowers T3 levels by decreasing the conversion of T4 to T3. Prazosin causes elevations in T4 and thyroid-stimulating hormone, while sodium nitroprusside use may result in hypothyroidism. Numerous agents are associated with sexual dysfunction, including methyldopa, reserpine, clonidine and spironolactone. Thiazide diuretics may cause hypercalcaemia, particularly in patients with hyperparathyroidism, by decreasing urinary calcium as well as directly influencing bone and gut calcium handling. Conversely, propranolol may decrease circulating parathyroid hormone levels and correct the hypercalcaemia seen in hyperparathyroidism. Awareness of drug-induced changes in endocrine function will facilitate the rational management of the hypertensive patient.

Effects of changes in endocrine function on water and electrolyte metabolism.

AbstractThe effects of a number of hormones on fluid and electrolyte balance are reviewed, first under normal physiological conditions and then under pathological conditions associated with loss of function or with overactivity due to the presence of hyperplasia or functioning tumors. Some of the most pronounced changes may occur with ectopic hormone production by certain neoplasms of nonendocrine origin.

Frontolateral hypothalamic knife cuts: Interruption of paraventricular efferents to the thoracolumbar cord

Bilateral thoracolumbar cord injections of the fluorescent tracer bisbenzimide produced extensive retrograde labelling of cell bodies in the paraventricular nucleus of the hypothalamus. Unilateral retrochiasmatic knife cuts (1.5 mm radius) located anterolateral to the paraventricular nucleus dramatically reduced or eliminated the labelling of paraventricular neurons on the ipsilateral side following bilateral bisbenzimide injections into the thoracolumbar cord. Thus paraventricular efferents to the thoracolumbar cord must project in a lateral direction at the level of the nucleus prior to descending toward the spinal cord. Changes in endocrine function, reproductive and feeding behavior reported following similar hypothalamic knife cuts may be related to this efferent system.

Effects of gossypol on pituitary-ovarian endocrine function, ovulation and fertility in female hamsters

Oral administration of gossypol acetic acid altered pituitary and ovarian hormones during proestrus and estrus in hamsters. These changes in endocrine function were not, however, accompanied by alterations of estrous cycle length, number of ovulations or pregnancy rates. Changes in body weight and appearance of the liver suggested that female hamsters may be more susceptible than males to the toxic effects of gossypol.

The treatment of essential hirsutism in women with cyproterone acetate and ethinyl estradiol. Clinical and endocrine effects in 10 cases.

Ten women with essential hirsutism were treated for one year with cyclic administration of cyproterone acetate and ethinyl estradiol. Biochemical and clinical control took place after 1, 3, 6 and 12 months of treatment. In 4 patients great improvement of hirsutism was noted, but only after 6 months of therapy. In 4 patients there was some improvement, while 2 were resistant. Side effects included reduced libido in 4 cases, mental depression in 3, dry skin and itching in 4 and transient nausea in one, but never necessitated cessation or interruption of treatment. Several changes in endocrine function took place during treatment: testosterone secretion rate diminished together with the urinary excretion of 17-KS and 17-KGS, while the serum concentration of testosterone binding globulin increased. There was a reduction in the serum concentration of total endogenous estrogens and progesterone as well as LH. No changes in hepatic, renal or hematologic parameters were found except for a slight increase in plasma prothrombin time. Clinical outcome of therapy could not be correlated with a pretreatment endocrine "profile", nor with the changes that this therapy induced in endocrine function. It is concluded that the anti-androgenic effect is probably the most important in this drug regimen, but that reversibility of hirsutism may depend upon factors not directly related to androgen influence.

An appraisal of radical pancreatoduodenectomy based on glucagon secretion.

In an attempt to elucidate changes in endocrine functions of the pancreas associated with radical pancreatectomy for periampullary cancer, plasma levels of insulin (IRI) and pancreatic glucagon (IRG) were measured during arginine infusion in ten patients with periampullary cancer both before and after pancreatoduodenectomy. The response of plasma IRI to arginine which was impaired before the surgery showed further impairment after the surgery. This finding is consistent with the previous results obtained in such patients by oral glucose tolerance testing. Also, the response of plasma IRG was subnormal preoperatively and was found to be impaired postoperatively. Both maximum and integrated secretion of IRG during arginine infusion decreased after the surgery in all instances. From these findings, it is concluded that pancreatoduodenectomy aggravates the already disordered pancreatic endocrine functions, as indicated by arginine infusion in patients with periampullary cancer.

1 Endocrine manifestations of systemic disease

1 Endocrine manifestations of systemic disease

Endocrine function before and after treatment in patients with anorexia nervosa (author's transl)

In order to investigate changes in endocrine function, various tests were performed on eleven patients with anorexia nervosa. In two of them, endocrine function before and after treatment was also studied. The responses of plasma LH and FSH to LH-RH were decreased in the patients as were plasma LH-RH, and LH and FSH responses to the oral administration of clomiphene citrate. In more than half of the cases, plasma TSH showed a delayed response to TRH. The basal levels of plasma GH were elevated, and plasma GH responses to hypoglycemia or 1-arginine were lowered in half of the patients. Plasma GH showed a paradoxical rise after glucose load in three out of six cases. Plasma IRI responses to 1-arginine load were decreased in some cases, but plasma IRG responses to 1-arginine were rather excessive. Plasma IRI after glucose load showed low or delayed responses in most of the cases. After the body weight was increased to normal levels by the treatment, pituitary and pancreatic endocrine functions were normalized. These findings indicate that hypothalamic function is primarily impaired in this disease and causes nutritional disorder followed by the dysfunction of some endocrine organs. Such a possibility could be supported by the improvement of endocrine function after body weight has been recovered.

Variation in activity of monoamine metabolizing enzymes in rat liver during pregnancy.

1. Catechol-0-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rat liver were measured during pregnancy, parturition and postpartum. Compared with activity in non-pregnant controls, both enzymes showed a significant decrease in activity which was most pronounced at day 18. 2. The metabolism of intravenously infused [3H]-adrenaline to [3H]-metanephrine and to [3H]-acidic metabolites was also significantly depressed during pregnancy but had returned to control values by the 21st day. 3. The effects of reserpine and/or nialamide on hepatic COMT and MAO were studied in control and 20-day-pregnant rats. Their action on COMT activity differed in the two groups. MAO was inhibited to a similar extent in these groups whether the drugs were given separately or in combination. 4. It seems possible that the changes in endocrine function which occur during pregnancy are responsible for the observed alterations in enzyme activity.

Endocrine Alterations In Delirium Tremens

A significant correlation was found between the psychopathological syndrome in delirium tremens and changes in endocrine function.

Hypothalamic releasing substances and inhibitors.

Control of anterior pituitary function by the hypothalamus, for which indirect evidence had been available for at least half a century, has now been placed on a firmer foundation with the discovery, isolation, and synthesis of a number of peptides possessing discrete stimulatory or inhibitory effects. These substances are synthesized in the hypothalamus and are transported to the vascular sinusoids of the adenohypophysis through a plexus of vessels extending down the pituitary stalk from the tuber cinereum. Hormones of the posterior pituitary, on the other hand, are transported along the axons of the hypothalamic hypophysial tracts to the neurohypophysis. Integration of the hypothalamus into the endocrine system has opened the door to the uncovering of the links between neural activity, such as rage, emotion, and sleep, and their effects on endocrine function. 1,2 The myriad of changes in endocrine function during sleep has been described recently in these pages and

Interrelated changes in host metabolism during generalized infectious illness

The metabolic effects of acute infectious illness in man involve virtually every biochemical pathway studied. For a number of years investigators in our Institute have worked systematically to define and provide a mechanistic explanation for the changes in host metabolism that accompany infection. Many such metabolic changes occur during only certain stages of a generalized infectious process. Some begin during the incubation period, others during the febrile period, and still others during convalescence. Some changes exhibit biphasic patterns in the course of their progression. For these reasons, serial measurements must be obtained throughout the course of an infection in order to understand the sequential process. Our initial studies in man (1-6) employed metabolic balance methods and were designed to describe infection-related changes in protein, electrolyte, and mineral metabolism as well as changes in endocrine functions. Tularemia, 0 fever, and sandfly fever were included in these studies as was an evaluation, in ancillary investigations, of the role of single pertinent variables such as fever, impaired dietary intake, increased secretion of adrenal glucocorticoid hormones, specific immunity, and antibiotic therapy.

Pharmacological Aspects of Neuroendocrine Integration

This chapter discusses the pharmacological aspects of neuroendocrine integration. Changes in endocrine function can be produced by drugs that act on the nervous system because a large segment of the endocrine system is under neural control. The link between the nervous system and the endocrine system appears in many instances to be adrenergic, or at least to have an adrenergic component in it. Circulating catecholamines and the catecholamines secreted at the endings of the renal nerves increase renin secretion by a mechanism involving a β -adrenergic receptor. Catecholamines inhibit insulin secretion by an α -adrenergic mechanism and stimulate it by a β- adrenergic mechanism. Hypothalamic catecholamines affect the secretion of most pituitary hormones, generally through receptors that are blocked by α -adrenergic blocking agents. Dopaminergic pathways stimulate follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion and inhibit prolactin secretion. Noradrenergic pathways stimulate growth hormone secretion and inhibit adrenocorticotropin hormone (ACTH) secretion. There is evidence that the secretion of thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH), oxytocin, and vasopressin are also regulated by catecholamine-containing neurons in the hypothalamus. The interactions between adrenergic mechanisms and the other unique factors that affect the secretion of renin, insulin, and the pituitary hormones merit further study.