Effects of ketoacidosis and puberty on basal and TRH-stimulated thyroid hormones and TSH in children with diabetes mellitus

Basal and TRH-stimulated thyroid hormones and TSH were evaluated in two groups of prepubertal and pubertal diabetics: group B - 45 children without ketoacidosis; group C - 16 children with ketoacidosis. The diabetic patients showed no signs of diabetic microangiopathy. Fifty-three healthy subjects served as controls (group A). T4, T3, FT4 and FT3 serum levels were reduced in diabetics, particularly in ketotic ones; T4 and T3 values were lower in pubertal than in prepubertal non-ketotic diabetics and in pubertal than in prepubertal controls, while no significant difference was observed between pubertal and prepubertal ketotic patients. Moreover, no difference in rT3 serum concentrations was found between group A, B and C, but non-ketotic and ketotic pubertals showed a significant rT3 reduction if compared with non-ketotic and ketotic prepubertals and with healthy pubertals. TBG was lower in group B and group C diabetics than in controls. After TRH stimulus, T3 levels showed a significant increase both in controls and in non-ketotic diabetics, while no variation was observed in ketotic children; furthermore, at 120 minutes T3 values were lower in diabetic than in healthy children, particularly in ketotic ones. Basal TSH serum concentrations were reduced in ketotic diabetics, while no difference was found between nonketotic and control subjects. After TRH stimulus, TSH peak was higher in pubertal non-ketotic diabetics than in pubertal controls, while no difference was found between prepubertal and pubertal diabetics, both in non-ketotic and in ketotic status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of neuropeptide Y on LH, FSH and TSH release in male rats

These experiments were undertaken to investigate the effects of systemically administered neuropeptide Y (NPY) on gonadotropin secretion in the intact male rat and to determine whether the effects observed might be mediated by a direct action of NPY alone on the anterior pituitary gland (APG). Subcutaneous administration of 10 micrograms of NPY caused a greater than 2-fold increase in serum luteinizing hormone (LH) concentration at 15 min after injection but was without effect on serum follicle-stimulating hormone (FSH) or thyrotropin-stimulating hormone (TSH) levels. The addition of NPY (final concentrations of 10(-8) to 10(-11) M) or the structurally similar neuropeptide, rat pancreatic polypeptide, to culture medium containing hemi-APG did not alter the release of LH, FSH, or TSH. The results indicate that systemically administered NPY can elevate serum LH concentration in intact male rats. This effect does not appear to be due to NPY acting alone at the level of the APG.     

Effects of intraventricular injection of gastrin on release of LH,prolactin, TSH and GH in conscious ovariectomized rats

Conscious ovariectomized (OVX) rats bearing a cannula implanted in the 3rd ventricle were injected with 2 μl of 0.9% NaCl containing varying doses of synthetic gastrin and plasma gonadotropin, GH and TSH levels were measured by RIA in jugular blood samples drawn through an indwelling silastic catheter. Control injections of saline iv or into the 3rd ventricle did not modify plasma hormone levels. Intraventricular injection of 1 or 5 μg gastrin produced significant suppression of plasma LH and prolactin (Prl) levels within 5 min of injection. Injection of 1 μg gastrin had no effect on plasma GH, but increasing the dose to 5 μg induced a progressive elevation, which reached peak levels at 60 min. By contrast, TSH levels were lowered by both doses of gastrin within 5 min of injection and the lowering persisted for 60 min. Intravenous injection of gastrin had no effect on plasma gonadotropin, GH and TSH, but induced an elevation in Prl levels. $\text{In}$$\text{vitro}$ incubation of hemipituitaries with gastrin failed to modify gonadotropin, GH or Prl but slightly inhibited TSH release at the highest dose of 5 μg gastrin. The results indicate that synthetic gastrin can alter pituitary hormone release in unrestrained OVX rats and implicate a hypothalamic site of action for the peptide to alter release of a gonadotropin, Prl and GH. Its effect on TSH release may be mediated both via hypothalamic neurons and by a direct action on pituitary thyrotrophs.     

Dopamine and TSH secretion in uremic male rats

The role of dopamine in the dysregulation of TSH secretion in uremic male rats was investigated using the dopamine antagonist, pimozide. In order to obviate the effect of weight loss due to uremia-induced anorexia as a cause of altered TSH secretion in uremia, we also studied a group of normal animals whose food intake was restricted and who demonstrated weight loss comparable to that of the uremic animals. Baseline TSH concentrations were not significantly different in the normal, uremic or starved animals. Pimozide administration produced no change in the baseline TSH concentrations in any of the groups of rats. The peak TSH response to TRH (5 micrograms IV) was significantly blunted in the uremic animals compared to the normal controls and the starved animals. Pimozide administration did not alter the peak TRH-stimulated TSH response in either the normal animals or the starved animals. However, the peak TRH-stimulated TSH response was significantly increased in the uremic animals and was comparable to the peak TSH response seen in the pimozide-untreated control animals. The data suggest that experimental renal failure in rats is associated with diminished sensitivity of the thyrotroph to TRH stimulation, and that this blunted sensitivity may be dopamine-dependent since it can be abolished by pharmacologic dopamine blockade.     

The effect of repetitive haemorrhage on plasma cortisol, beta-endorphin and N-terminal pro-opiomelanocortin in conscious sheep

We measured the effect of repeated haemorrhagic stress, performed on four consecutive days in conscious adult sheep, on the plasma concentrations of cortisol and ACTH-related peptides to determine whether the pituitary-adrenal response was altered by stress repetition. Peptides from the C-terminus of the ACTH pro-hormone was measured by beta-endorphin RIA. Glycopeptides derived from the N-terminus of the ACTH pro-hormone were measured by tau 3-MSH RIA. The immunoreactive tau 3-MSH in sheep plasma was found to have an apparent molecular weight of approximately 10,000 by gel chromatography through Sephadex G-75, which is similar to the size of the major circulating form of pro-tau-MSH found in human and rat plasma. Daily haemorrhage consistently elevated plasma concentrations of cortisol and pro-tau-MSH. There was no significant difference in the daily responses of either cortisol or pro-tau-MSH when considered individually. However, there was a significant change over the four days in the relationship between the cortisol and pro-tau-MSH responses, as judged by analysis of variance of the difference in daily z-scores of cortisol and pro-tau-MSH. This trend indicated a relative increase in the secretion of pro-tau-MSH from the pituitary compared to the cortisol response, and suggested that repeated exposure to stressful stimuli may alter the pituitary-adrenal-axis.     

A giant prolactinoma and the effect of chronic bromocriptine therapy on basal and TRH-stimulated serum prolactin levels.

The role of bromocriptine as primary therapy for prolactin-producing tumors is currently well accepted in the literature. Bromocriptine decreases the concentration of serum prolactin and this decrease precludes tumor shrinkage, despite the lack of correlation between amount of decrease in tumor size and baseline serum prolactin. We submit the case of a patient on chronic bromocriptine therapy followed by measuring baseline and thyrotropin-releasing hormone (TRH)-stimulated serum prolactins. Bromocriptine affects both release and storage of prolactin. The literature has suggested that the effects of bromocriptine on storage and synthesis may be responsible for its effects on tumor size. It was felt that TRH stimulation would more accurately reflect storage and synthesis, and thus correlate better with tumor size. The pituitary was initially debulked via a right frontal approach; then the patient was placed on bromocriptine therapy and postoperatively followed with baseline and TRH-stimulated serum prolactins. The size of the pituitary was measured by computed tomography. Baseline serum prolactin levels rapidly decreased, but despite the slow decrease in TRH-stimulated prolactins no change was noted in tumor size. Because of the time difference between the baseline and TRH-stimulated prolactin levels, we conclude that clinically bromocriptine affects primarily secretion of prolactin and secondarily storage and synthesis. We also show that TRH-stimulated prolactin does not correlate with size of prolactin-secreting pituitary tumors and therefore tumor size should be independently measured. The literature has shown that prolactinomas do not respond well to TRH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of alfuzosin on urethral and blood pressures in conscious male rats

This study was undertaken to determine simultaneously the effects of Alfuzosin on urethral and blood pressures in the same conscious male rat. Alfuzosin (i.v., 3, 10 and 30 μg/kg) dose-dependently decreased urethral pressure without affecting mean arterial blood pressure. At the higher dose, blood pressure was only slightly and transiently decreased while a marked decrease (−40%) in urethral pressure was observed. Therefore, this experimental model is suitable to assess uroselectivity.     

Effect of third ventricular injections of prostaglandins (PG's) on gonadotropin release in conscious free moving male rats

Prostaglandin E₂ (PGE₂) (5 μg in 5 μl) injected into the third ventricle (3rd V) of intact or castrated conscious male rats markedly increased plasma LH titers 15 and 30 min after its injection. PGE₁ injected at a similar dose slightly increased plasma LH in intact but not in orchidectomized rats. A small but significant increase in plasma FSH followed 3rd V injection of both PGE₂ and PGE₁ in intact but not in castrated rats. PGF_1α and PGF_2α were completely ineffective in modifying plasma LH or FSH titers in either intact or castrated rats. These results indicate that PGE₂ and to a lesser extent PGE₁ specifically stimulate gonadotropin release in the male rat, possibly by a direct action on the central nervous system. They also support the hypothesis that PGE₂ and perhaps PGE₁ play a physiological role in neural control of pituitary gonadotropin release.     

Preference for dietary fat induced by release of beta-endorphin in rats

AimsTo determine whether beta-endorphin contributes to the ingestion of and preference for dietary oil, we examined the relationship between the dynamics of beta-endorphin, before and after the ingestion of corn oil, and the intake volume of corn oil.Main methodsRats were offered 5% corn oil for 20 min for 5 consecutive days so they could acquire a preference for corn oil. On day 6, seven groups of rats were presented with the oil for defined time periods, and we measured the beta-endorphin levels in the serum and cerebrospinal fluid (CSF) before and after the presentation of corn oil as well as the consumed volume of corn oil at defined time points.Key findingsBeta-endorphin levels in serum and CSF were significantly increased 15 min after the ingestion of corn oil, followed by a rapid decrease and maintenance at the basal level throughout the rest of the experimental period. The intake of corn oil was the lowest in the time period of 15–30 min, when the beta-endorphin level reached a peak value. The intake volume of corn oil might be inversely correlated with beta-endorphin levels in serum and CSF. The pretreatment of naloxone, an antagonist of the opioid receptor, decreased the initial licking rate for corn oil and increased the latency for corn oil in the licking test.SignificanceThe beta-endorphin was rapidly released after oil ingestion, which contributed to the hedonic preference and ingestive behavior for fat.     

17beta-estradiol stimulates ascorbic acid and LHRH release from the medial basal hypothalamus in adult male rats

In the present investigation, 17beta-estradiol (E(2)) and tamoxifen, an antiestrogen, were evaluated for their effects on the release of ascorbic acid (AA) and luteinizing hormone-releasing hormone (LHRH). Medial basal hypothalami (MBH) from adult male rats were incubated with graded concentrations of E(2) (10 (-9) to 10(-6) M) or a combination of E(2) (10(-7) M) and tamoxifen (10(-7) and 10(-6) M ) in 0.5 ml of Krebs Ringer bicarbonate buffer for 1 hr. AA and LHRH in the incubation medium were measured by high-performance liquid chromatography and radioimmunoassay, respectively. E(2) significantly elevated both AA and LHRH release and the minimal effective dose was 10(-7) M. A combination of E(2) (10(-7) M) and tamoxifen (10(-6) M) totally blocked E(2)-induced AA and LHRH release. The stimulatory effect of E(2) was also suppressed in the presence of N(G)-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase (NOS), illustrating that the release is mediated by nitric oxide (NO). To further characterize the role of NO, the tissues were incubated with E(2) or a combination of E(2) + (6 anilino-5, 8-quinolinedione) LY 83583 (10(-6) and 10(-5) M), an inhibitor of NOS. LY 83583 was effective in suppressing E(2)-induced AA and LHRH release, demonstrating that the effect was mediated by cyclic GMP. Incubation of the tissues with E(2) or a combination of E(2) + 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (O.D.Q.) (10(-5) and 10(-4) M), a specific inhibitor of soluble guanylyl cyclase failed to alter AA release but significantly suppressed LHRH release. The role of a prostaglandin synthesis blocker in E(2)-induced AA and LHRH release was tested by incubating the tissues with E(2) or a combination of E(2) + indomethacin (1.8 x 10 (-7) or 1.8 x 10(-6) M). Indomethacin produced a significant decrease in E(2)-induced AA and LHRH release, suggesting that the release process required prostaglandins as an intracellular mediator. In conclusion, E(2) stimulated both AA and LHRH release and the effect was mediated by NO and prostaglandins.     

The effect of chronic estrogen treatment on immunoreactive beta-endorphin levels in intact female rats

Intact female rats were treated chronically with estradiol benzoate (EB) until a state of constant estrus (CE) was achieved and maintained. When compared to female rats on the day of estrus, estrogen-treated rats in constant estrus demonstrated a 33% decrease in the concentration of immunoreactive beta-endorphin (IR-BE) in the plasma, and a 45-50% decrease in the content and concentration of IR-BE in the anterior pituitary and hypothalamus. The content and concentration of IR-BE in the neurointermediate lobe of the pituitary were similar in each group. Column chromatography revealed that the reduction in IR-BE in the plasma and anterior pituitary of EB-treated CE female rats appeared to be due to a reduction in peptides coeluting with beta-endorphin and beta-lipotropin, whereas the reduction in IR-BE in the hypothalamus represented a decrease in a peptide which coeluted with beta-endorphin. These data suggest that constant estrus, induced by prolonged treatment of intact female rats with estrogen, resulted in a reduction in central and peripheral levels of IR-BE in these animals as compared to female rats on the day of estrus.     

The biphasic selective effect of an antiserum to beta-endorphin on pain sensitivity in rats

In rats beta-endorphin antiserum systemic injection decreased during 1-2 days the threshold of tail-shock and latency of tail-flick tests, and during subsequent 85 days increased the threshold of tail shock, but not changed the latency of tail-flick tests. Naloxone injection blocked the increasing of thresholds, but not changed the latency of tail tests. It is suggested that antiserum evokes the first inhibition and the second selective activation of endogenous antinociceptive opioid system with affinity to electric nociception.     

Changes in immunoreactive basic somatomedin in conscious and anaesthetized male rats

Basic somatomedin (B-SM) like insulin-like growth factor-I or somatomedin-C belongs to the basic group of somatomedins. In preliminary studies on the control system for B-SM, we have found that plasma levels of immunoreactive B-SM (IRSM) fluctuate in conscious adult male rats. The peaks average 85% of the local baseline level (minimum of 6 points) and occur with an interpeak interval of 2.1 h. In rats anaesthetized with nembutal (50 mg/kg) very few peaks were found. After approximately 3.4 hr. of anaesthesia, plasma IRSM levels dropped precipitously with a calculated T1/2 of 50 minutes. These results suggest that IRSM levels may be related to serum CH levels which occurred 4 hr previously and that part of variation seen in serum levels in conscious rodents may be due to physiological fluctuations.     

Diurnal variations of medial basal and anterior hypothalamic thyroliberin [TRH] and serum thyrotropin [TSH] concentrations in male rats.

The diurnal variation of TRH concentrations in different parts of hypothalamus was studied in 80 male rats, which were killed in groups of 5 at 3 h intervals. The hypothalamus was dissected into three parts: I) medial basal hypothalamus (MBH), II) anterior hypothalamus, and III) dorsal hypothalamus. Anterior pituitary and serum TSH concentrations were also measured. TRH concentrations were higher in MBH than in the other parts of the hypothalamus: at night 300–450 pg/mg of wet weight of tissue. When the lights were turned on, MBH-TRH levels began to decrease, reaching a nadir of 210 pg/mg at 12 noon. After 15 h, MBH-TRH levels began to increase again. The changes in TRH levels in anterior hypothalamus were usually opposite to those in MBH (r = ?0.6185). Serum TSH levels were about 800 ng/ml during the day and were decreased to about one half of these levels when the lights were turned off. Serum TSH levels were positively correlated with anterior hypothalamic TRH levels (r = 0.6457) and inversely correlated with MBH-TRH levels (r = ?0.7747). Anterior pituitary TSH levels showed small but statistically insignificant variations. In conclusion, there were statistically interrelated diurnal rhythms in anterior hypothalamic and MBH-TRH levels and serum TSH concentrations.     

Thyroid stimulating hormone and prolactin secretion: reduced sensitivity to TRH-stimulated prolactin release after midpregnancy in rats

Prolactin (PRL) and thyroid stimulating hormone (TSH) plasma concentrations were measured during the latter part of the dark period in early and mid-late pregnancy in the rat. On Days 4-5 and 7-8 of pregnancy, plasma PRL concentrations surged between 22:00 and 06:00 hr and TSH values increased between 22:00 and 02:00 hr. While the TSH pattern was maintained during the second-half of pregnancy, surges in PRL release ceased and PRL levels remained at less than 10 ng/ml. The effects of thyrotropin releasing hormone (TRH) administration on PRL and TSH secretion were then measured to determine whether the second-half of pregnancy is associated with a decrease in sensitivity to an agent that can stimulate PRL release. Injection (iv) of cannulated pregnant rats with a low dosage (20 ng) of TRH stimulated a twofold increase in plasma TSH during both early (Days 5-9) and later (Days 14-18) pregnancy but did not change plasma PRL levels. Treatment with a high dosage (2 micrograms) of TRH induced a sixfold rise in plasma TSH during both phases of gestation. The higher dose of TRH also stimulated elevations in plasma PRL during early and mid-late pregnancy; however, both the absolute increase in the amount of PRL in plasma and the percentage increase over baseline levels were greater from Days 5-9 than from Days 14-16 of gestation. These data indicate that the neuroendocrine sensitivity to factors that stimulate PRL secretion changes as pregnancy progresses, and suggest that nocturnal secretion of PRL and TSH during pregnancy may be regulated, in part, by a common trophic factor.