Endocrinological Manipulations Research Articles

Plasticity of neuroendocrine–thymus interactions during ontogeny and ageing: Role of zinc and arginine

Thymic re-growth and reactivation of thymic functions may be achieved in old animals by different endocrinological or nutritional manipulations such as, (a) treatment with melatonin, (b) implantation of a growth hormone (GH) secreting tumour cell line (GH3 cells) or treatment with exogenous GH, (c) castration or treatment with exogenous luteinizing hormone-releasing hormone (LHRH), (d) treatment with exogenous thyroxin or triiodothyronine, and (e) nutritional interventions such as arginine or zinc supplementation. These data strongly suggest that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine–thymus interactions and that it is the disruption of these interactions in old age that is responsible for age-associated immune–neuroendocrine dysfunctions. The targets involved in hormones-induced thymic reconstitution may directly or indirectly involve hormone receptors, cytokines, arginine, and a trace element such as zinc, which is pivotal for the efficiency of neuroendocrine–immune network during the whole life of an organism. The effect of GH, thyroid hormones, and LHRH may be due to specific hormone receptors on thymocytes and on thymic epithelial cells (TECs), which synthesize thymic peptides. Melatonin may also act through specific receptors on T-cells. In this context, the role of zinc, which turnover is reduced in old age, is pivotal because of its involvement through zinc fingers in the gene expression of hormone receptors. In addition, the effects of zinc are multifaceted: from the reactivation of zinc-dependent enzymes, to cell proliferation and apoptosis, to cytokines expression and to the reactivation of thymulin, which is a zinc-dependent thymic hormone required for intrathymic T-cell differentiation and maturation as well as for the homing of stem cells into the thymus. Zinc is also required for arginine action, via NO pathway. The role of zinc is therefore crucial in neuroendocrine–thymus interactions. According to data in animals and humans, the above reported endocrinological manipulations (GH, thyroid hormones, and melatonin) or arginine treatment may also act via zinc pool in restoring thymic activity in ageing allowing improvements on peripheral immune efficiency.

Plasticity of neuroendocrine-thymus interactions during aging.

Thymic regrowth and reactivation of thymic endocrine activity may be achieved even in old animals by different endocrinological or nutritional manipulations such as, (a) intrathymic transplantation of pineal gland or treatment with melatonin, (b) implantation of a growth hormone (GH) secreting tumor cell line or treatment with exogenous GH, (c) castration or treatment with exogenous luteinizing hormone-releasing hormone (LH-RH), (d) treatment with exogenous thyroxine or triiodothyronine, and (e) nutritional interventions such as arginine or zinc supplementation. These data strongly suggest that thymic, involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of such interactions in old age that is responsible for age-associated dysfunction. With regard to the mechanisms involved in hormone-induced thymic reconstitution, it is at present, difficult to draw any definitive conclusions. The effect of GH, thyroid hormones, and LH-RH may be due to the presence on thymic epithelial cells supposed to produce thymic peptides, of the specific hormone receptors. Melatonin or other pineal factors may also act through specific receptors, but experimental evidence is still lacking. The role of zinc, whose turnover is usually reduced in old age, is diverse. The effects range from the reactivation of zinc-dependent enzymes, required for both cell proliferation and apoptosis, to the reactivation of thymulin, a zinc-dependent thymic hormone. The role of zinc may even be more crucial. According to recent preliminary data obtained both in animal and human studies, it appears that the above reported endocrinological manipulations capable of restoring thymic activity in old age, may act also by normalizing the altered zinc pool.

Independent steroid control of the fates of motoneurons and their muscles during insect metamorphosis

The metamorphosis of insects is controlled by the blood titers of a small number of developmental hormones including a class of steroids, the ecdysteroids. We have studied the developmental fates of several muscles and their motoneurons during the larval-pupal transformation of the tobacco hornworm, Manduca sexta. The endocrine events which trigger pupal development are first, a fall in the blood titer of juvenile hormone, followed by two subsequent elevations of blood ecdysteroids. The small "commitment pulse" of ecdysteroids commits tissues to pupal development, whereas the sustained "prepupal peak" causes the new pupa to be formed (Riddiford, L. M. (1980) In Progress in Ecdysone Research, J.A. Hoffmann, ed., pp. 409-430, Elsevier/North-Holland Biomedical Press, Amsterdam). In the present experiments we were able to correlate specific aspects of the changing blood steroid titers with the degeneration of larval muscles, and with the dendritic regression and death of their motoneurons. The abdominal prolegs, which are the principal locomotory appendages of the caterpillar, are lost during the larval-pupal transformation. We have followed the fates of a proleg retractor muscle, PPRM, and its single motoneuron, PPR. Two other differently fated abdominal muscles not associated with the proleg were also studied. Surgical and endocrinological manipulations showed that PPRM degenerates in response to the rising phase of the prepupal ecdysteroid peak and that interactions with its motoneuron are not involved in the muscle's death. Motoneuron PPR responds to the rising prepupal peak by first reducing its dendritic arbor by 40% and then dying. Other proleg motoneurons regress but do not die, indicating that dendritic regression is programmed separately from neuronal death. Neither the dendritic reduction nor the death of PPR involves interactions with its target muscle. These results indicate that ecdysteroids have independent and parallel effects in the periphery, where they cause muscle degeneration, and in the central nervous system, where they cause dendritic regression and death of motoneurons.

Endocrine control of thymic serum factor production in young-adult and old mice

The influence of different endocrinological manipulations on the blood concentration of serum thymic factor (FTS) was studied in young-adult and old mice. Among the experimentally induced endocrinopathies in youth, hypothyroidism and diabetes caused strong reductions of FTS levels, which were restored to normal by the appropriate hormonal substitutive therapy. Removal of adrenals or gonads has no significant effect on FTS level. Old mice, which show undetectable levels of FTS and low levels of thyroxine, can regain the capacity to produce FTS, provided they are treated with thyroxine. The variations of FTS blood levels in the course of endocrinological manipulations were due to a direct or indirect effect exerted on the recipient thymus. Hormonal treatment of thymectomized mice did not induce any FTS-like activity in their sera, nor did hormones interfere in vitro with the bioassay used to test for FTS. These data suggest that the neuroendocrine balance modulates the synthesis and/or the release of FTS from the thymus during the whole life of the organism and that the decline of FTS production with advancing age is largely dependent on age-associated endocrinological imbalances.

Catecholaminergic neurons projecting from the ventrolateral medulla oblongata to the preoptic and anterior hypothalamic areas: Their neural activity after various endocrinological manipulations

Catecholaminergic neurons projecting from the ventrolateral medulla oblongata to the preoptic and anterior hypothalamic areas: Their neural activity after various endocrinological manipulations

Catecholaminergic neurons projecting from the ventrolateral medulla oblongata to the preoptic and anterior hypothalamic areas: Their neural activity after various endocrinological manipulations

Catecholaminergic neurons projecting from the ventrolateral medulla oblongata to the preoptic and anterior hypothalamic areas: Their neural activity after various endocrinological manipulations

Vasopressin and oxytocin in the rat spinal cord: Distribution and origins in comparison to [met]enkephalin, dynorphin and related opioids and their irresponsiveness to stimuli modulating neurohypophyseal secretion

Immunoreactive-vasopressin, -oxytocin, -dynorphin, -dynorphin-(1–8), -α-neo-endorphin and -[Met]enkephalin were, in each case, present in greater concentrations in dorsal as compared to ventral, and lumbo-sacral as compared to cervico-thoracic, spinal cord. These differences were significantly more pronounced for vasopressin and oxytocin than for the other peptides. Lesions of the hypothalamic paraventricular nucleus depleted levels of immunoreactive-vasopressin and -oxytocin throughout the cord whereas levels of the opioid peptides therein were unaffected. In contrast, destruction of either the supraoptic or suprachiasmatic nucleus failed to change the content of immunoreactive-vasopressin, -oxytocin or any of the opioid peptides in the cord. Dehydration for 3 days depressed levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate lobe of the pituitary. In distinction, the levels of these were not modified in the spinal cord. Further, treatment with the synthetic corticosteroid, dexamethasone, elevated levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate pituitary whereas these were unaffected in the spinal cord. It is concluded that vasopressin and oxytocin in the spinal cord are predominantly derived from the paraventricular nucleus, localized in dorsal lumbo-sacral regions of the cord and insensitive to endocrinological manipulations. These pools may, thus, be modulated differently from their counterparts in the neurohypophysis and have a differing role, possibly in the control of the primary processing, autonomic or motor junctions. Further, there is no evidence from these or our prior studies 25a,26 for a close interrelationship of spinal cord vasopressin with dynorphin-related peptides (or oxytocin with [Met]enkephalin), likewise in contrast to the neurohypophysis. A general independence of spinal cord pools of vasopressin and oxytocin from their neurohypophyseal counterparts may be concluded.

Effect of reserpine, 5-hydroxytryptamine and endocrinological manipulations on ovarian maturation of a marine crab

An increase was observed in the ovarian index inScylla serrata following administration of reserpine (a neuroleptic), but there was no change after 5-hydroxytryptamine administration. The releasing and inhibiting mechanisms for reproductive hormones ofS. serrata are discussed.

Tyrosine hydroxylase regulation in the central nervous system.

Tyrosine hydroxylase is considered to be the rate-limiting enzyme in the synthesis of catecholamines in both the central and peripheral nervous system. Increased or decreased neuronal activity, stress, lesions, drug effects, endocrinological manipulations and experimental models of hypertension are associated with alterations in tyrosine hydroxylase activity in the central nervous system. In many of these instances, the changes in the activity of tyrosine hydroxylase in the central nervous system that occur are localized to discrete catecholaminergic pathways and nuclei in the brain. The purpose of this review is to summarize and assess this information and to provide insight into the function of catecholamine systems in the brain and their interactions with other putative neurotransmitter systems.

Norepinephrine and dopamine turnover rates in the medial preoptic area and the mediobasal hypothalamus of the rat brain after various endocrinological manipulations.

Norepinephrine (NE) and dopamine (DA) turnover rates were measured in the medial preoptic area (MPO) and in the anterior and posterior mediobasal hypothalamus (AMBH and PMBH) in groups of rats subjected to various endocrinological manipulations. NE turnover in the MPO was high in proestrous, ovariectomized, ovariectomized estrogenprimed, and ovariectomized, estrogen-primed, progesteronetreated rats when the experiments were carried out during afternoon hours. Diestrous rats had low NE turnover rates in the MPO. The NE turnover rate was also low when measured in ovariectomized, estrogen-primed animals decapitated in the morning. These turnover rates parallel low serum LH levels. NE turnover in the AMBH and PMBH was low in diestrous and ovariectomized animals during afternoon hours and was also low in ovariectomized estrogen-primed rats during morning hours. High NE turnover rates in these structures were measured in proestrous, ovariectomized, estrogen-primed and estrogenprimed, progesterone-treated rats k...

Electrophysiological studies on the development and sex differentiation of the brain systems controlling gonadotropin secretion in immature rats (author's transl)

In order to elucidate the process of the development and sex differentiation of the brain systems controlling gonadotropin secretion, electrophysiological studies were performed using immature intact rats of both sexes after endocrinological manipulations. Medial preoptic (MPO) unit responses to the medial amygdala (AMYG) or the dorsal hippocampus (HPC) stimulation (0.1-2.0mA, 0.2msec, 2/3Hz) and hypothalamic arcuate (ARC) unit reponses to the MPO stimulation were examined by means of post-stimulus time histograms, and percentages of neurons responding in a facilitatory or in an inhibitory manner and threshold currents for the induction of the unit response were calculated. Furthermore, the effects of gonadectomy and estrogen administration on serum gonadotropin concentrations were examined in immature female rats of various ages.Intact rats were classified into 4 groups : i.e., 21-25, 26-30, 31-35 and 36-40 days of age. Neither responses of ARC neurons to the MPO stimulation nor thresholds of the MPO stimulation for the induction of the ARC unit responses showed any significant differences during prepuberal growth nor between sexes. In male rats, the percentages of MPO neurons which were facilitated by the AMYG stimulation decreased during the development (x2=11.963), while the change in percentages of MPO units responding to the stimulation in female rats was rather small (x2=4.053). Significant developmental changes were observed in the percentages of MPO units responding to the HPC stimulation in both males (x2 = 39.957, p<0.001) and females (x2=15.628, p<0.02). Moreover, differences in the number of MPO units responding to the HPC stimulation were observed between intact 21-25-day-old male and female rats (p<0.02), between neonatally (at 2 or 3 days of age) gonadectomized 21-25-day-old males and females (p<0.005), and between neonatally gonadectomized and intact 21-25-day-old males (p<0.05), though responsive patterns of the MPO units to the AMYG stimulation were not significantly different between both sexes except at the age of 31-35 days (p<0.05).Thresholds of the AMYG stimulation for the induction of the MPO unit responses were lowered and those of the HPC stimulation elevated during development in both sexes. Estrogen injection at weaning lowered the threshold of the AMYG, and elevated that of the HPC in female rats. Testosterone injection at weaning in male rats lowered the HPC threshold. In rats which had been gonadectomized at weaning, thresholds of the HPC stimulation were significantly lower and those of the AMYG stimulation higher than in intact rats of the same age.Endocrinologically, a simultaneous injection of estrogen with ovariectomy caused a significant and transient increase in serum gonadotropin concentrations 1 day after the treatment in 40-day-old female rats, 2 days after in 30-day-old rats, and 3 days after in 25day-old rats.These results showed the existence of sexual differences and developmental changes in the limbic-preoptic neural transmissions. It was suggested that the AMYG-MPO system might develop after weaning, presumably under the influence of gonadal hormones, and the lowering in thresholds of the AMYG stimulation during maturation or following estrogen treatment in female rats might be related to the development of stimulatory feedback mechanisms of estrogen which induce phasic gonadotropin release indispensable for ovulation in mature female rats. The HPC-MPO system might have a sexual dimorphism before the age of 20 days, and testes at very early periods of life as well as during postnatal growth might have an important role in the development of HPC-MPO mechanisms in the male. In female rats, estrogen might reorganize the role of the HPC, which had been a trigger for the initial FSH release for ovarian growth in the early prepuberal period,

The effect of endocrinological manipulations on tyrosine hydroxylase and dopamine-beta-hydroxylase activities in individual hypothalamic nuclei of the adult male rat.

Using a recently developed microdissection method, individual hypothalamic nuclei were removed from the brains of adult male rats, and the tyrosine hydroxylase (TH) and dopamine-β- hydroxylase (DBH) activities in each nucleus were determined 9 days after adrenalectomy, thyroidectomy or gonadectomy. Following gonadectomy there was a significant rise in the TH activity in only the median eminence (ME). This increased TH activity was partially reversed by treatment of gonadectomized animals with testosterone. Thyroidectomy induced a significant increase in the TH activity in the ME, the dorsomedial (NDM), the periventricular (NPE) and the arcuate (NARC) nuclei. Twelve hr after administration of thyroxine, the TH activity in the ME of thyroidectomized rats was significantly reduced to levels below those of controls, whereas the TH activities of the other nuclei were returned to control values. Adrenalectomy produced a significant fall in TH activity in the ME, whereas dexamethasone significantly increased the...