Role of thyrotropin-releasing hormone in thyroid-stimulating hormone and growth hormone regulation during postnatal maturation in female Wistar rats

The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-stimulating hormone (TSH) and growth hormone (GH) secretion was studied during postnatal maturation in female Wistar rats. Half of the sucklings in each litter was treated intraperitoneally with either specific rabbit antiserum against TRH or normal rabbit serum (0.1-0.3 ml according to age). All animals were decapitated after 2 h. The presence of anti-TRH activity was checked as a binding of labelled TRH with plasma of the experimental animals. Immunoneutralization of endogenous TRH resulted in a decrease of plasma TSH in 3- to 15-day-old female pups as compared to control littermates. No effect of TRH antibody injection was seen at the ages of 1, 21, 30 and 70 days despite the presence of excess antibody in the plasma. A profound effect of TRH antibody on plasma TSH was seen again at the age of 100 days. Plasma GH in the same animals exhibited a paradoxical increase after TRH immunoneutralization at the age of 5 and 8 days, a decrease was found at the age of 21 days. It was concluded that hypothalamic TRH control of TSH secretion matures early in Wistar rats. Hypothalamic secretion of TRH at the ages of 1, 21, 30, and 70 days is low and(or) its role in TSH regulation is masked by other regulating factors. TRH may play a dual role in the regulation of GH secretion during the postnatal period.     

Prolactin response to exercise,metoclopramide and other provocative agents in children

Metoclopramide (MCP), a derivative of procainamide was compared with exercise, arginine, insulin and thyrotropin releasing hormone (TRH) as a prolactin (PRL) releaser in children. The peak response of plasma PRL after oral administration of MCP was greater than that after strenuous exercise and after i.v. administration of pharmacodynamic agents. Normal PRL and TSH responses were observed after TRH administration in all subjects. Variable PRL responses were seen after exercise and after i.v. administration of arginine and insulin, despite significant growth hormone (GH) release following the administration of these agents. MCP produced no increase in plasma TSH. Metoclopramide may be useful for dynamic testing of PRL release in children. It can be taken orally and is free of side-effects.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

Prolactin secretion in 70 patients with growth hormone deficiency

The basal levels of prolactin (PRL) and its response to TRH stimulation were studied in 70 patients with growth hormone deficiency of various etiology. It was found that there was a low secretion of PRL which was in most cases associated with a low response of TSH to TRH as well in 8 (36%) of 22 patients with so-called isolated growth hormone deficiency (IGHD) and 3 of 21 patients with multiple pituitary hormone deficiencies (MPHD). On the basis of this observation it is suggested that IGHD patients found to have a deficiency of PRL be reclassified as suffering form MPHD due to pituitary disease. High basal levels of PRL, usually associated with a delayed response of TSH to TRH, were found in 2 patients with IGHD and in 8 with MPHD (prior to substitution therapy with thyroxine) in whom the deficiency is probably: due to disease of the hypothalamus. With two exceptions the PRL levels normalized in the MPHD patients following institution of thyroxine replacement treatment. In the idiopathic cases of GH deficiency the determination of PRL levels was therefore found to be useful in delineating the location of the defect and in correctly classifying individual patients. Among the patients with tumors a disturbance in PRL secretion was found preoperatively in 4 of the 6 cases studied, the low PRL response in 2 being suggestive of a pituitary disturbance. Post-operatively evaluation of the PRL secretion was found useful in assessing the completeness of hypophysectomy and the persistence or recurrence of the tumor.Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 65th birthday     

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH-RETARDED CHILDREN TREATED WITH GROWTH HORMONE: II. Secretion of LH, FSH, TSH, Prolactin and ACTH

Abstract. P. C. Eskildsen, B. B. Jacobsen, K. W. Kastrup, S. Krabbe, P. E. Lebech and K. E. Petersen (The Children's Hospital Fuglebakken, Herlev Hospital and Frederiksberg Hospital, Copenhagen, Denmark). Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. Acta Paediatr Scand, Suppl. 277: 14, 1979.—A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T₄, T₃, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.     

Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus]

In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease.     

Thyrotropin and prolactin response to thyrotropin-releasing hormone in healthy and asphyxiated full-term neonates

To evaluate the effect of perinatal asphyxia on the pituitary response to thyrotropin-releasing hormone (TRH) in full-term newborn infants, serum thyrotropin (TSH) and prolactin (PRL) levels were measured before and 30 and 180 min after i.v. administration of 40 micrograms TRH. Birth weight, gestational and postnatal age were similar in the healthy (group NA) and in the asphyxiated (group A) babies. Hormone levels were determined by radioimmunoassay using commercial kits. It was demonstrated that the basal TSH level was slightly higher and the basal PRL level significantly (p less than 0.05) higher in group A than in group NA. In response to TRH administration in group A a marked increase in PRL occurred from 6781 +/- 887 to 11 072 +/- 1318 and 9636 +/- 1024 mU/l at 0, 30 and 180 min, respectively. A similar response was seen in group NA; the values, however, remained significantly lower during the TRH-test. The respective PRL values at 0, 30 and 180 min were 4672 +/- 411, 7945 +/- 343 (p less than 0.05) and 5963 +/- 372 mU/l (p less than 0.05). TRH administration also resulted in a significant elevation of the serum TSH level from 6.20 +/- 1.30 to 49.02 +/- 7.25 (p less than 0.01) and 18.72 +/- 6.35 mU/l (p less than 0.05) in group A, and from 3.90 +/- 0.57 to 24.01 +/- 3.81 (p less than 0.01) mU/l in group NA, but in group NA the 180 min TSH value of 6.07 +/- 1.25 mU/l did not differ statistically from the basal level (p greater than 0.1). It is concluded that the pituitary PRL and TSH reserves are maintained in full-term newborn infants recovering from perinatal asphyxia whose biochemical findings are indicative of subclinical hypothyroidism.     

The effects of intranasally sprayed synthetic TRH on TSH and on PRL secretion in children

The effects of intranasally applied TRH on serum TSH and PRL were investigated in ten healthy, prepubertal children. Serum levels of T4, T3, TSH, and PRL were all in the normal range. Synthetic TRH, 500 micrograms, in water was insufflated in one nostril. Intranasal TRH induced a prompt rise of TSH and PRL in all children with peak values at 30 min. TSH: 10.29 +/- 1.24 microU/ml; PRL: 25.12 +/- 3.53 ng/ml (mean +/- SEM). TSH values were still significant raised 120 min after the insufflation (P less than 0.025) whereas the PRL values did not differ significantly. A dose-dependent TSH release following intranasal sprayed TRH was shown. delta TSH and TSH values at 120 min were significantly higher in children receiving greater than 10 micrograms/kg TRH than in children receiving less than 10 micrograms/kg (P less than 0.025; P less than 0.05). Dose dependent differences in PRL release following intranasal TRH were not shown. Any side effects of intranasally applied TRH were not observed. Intranasal insufflation of synthetic TRH seems to be a valuable and harmless tool for the evaluation of pituitary TSH and PRL secretory reserve.     

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.     

Response to TRH in suspected hypopituitarism.

A retrospective analysis was made of 405 thyrotrophin-releasing hormone (TRH) stimulation tests on children who were successful applicants for growth hormone (GH) therapy in the UK between 1977 and 1981 inclusive. Thyroid-stimulating hormone (TSH) responses to TRH were divided into normal and those indicating pituitary or hypothalamic disease on the basis of criteria which eliminated variation in TSH assay between laboratories. Among children known to be hypothyroid 93% had abnormal TRH stimulation tests, but 35% of those children who were clinically euthyroid and who had normal serum thyroxin levels also had abnormal TSH responses to TRH. Abnormal TRH tests in the latter group were most common in euthyroid children who had GH deficiency with clearly defined aetiology and least common in those with idiopathic GH deficiency. Further work is required to clarify the interpretation of an abnormal TRH stimulation test in this group of children, but until this is done, such patients should be kept under regular review with respect to thyroid function.     

TSH and PRL response to thyrotrophin-releasing hormone in children with chronic renal failure undergoing haemodialysis.

Eight children (aged between 8 1/2 and 15 1/2 years) with chronic renal failure receiving intermittent haemodialysis, and 2 children with renal transplants were studied. The response of TSH and prolactin (PRL), and basal T4 and T3 values was measured. Basal TSH was normal, and rose only slightly after TRH stimulation. Plasma T4 and T3 were below normal levels in 6 children. Mean basal PRL was raised and could not be stimulated by TRH. This study demonstrates the involvement of the hypothalamus and pituitary in chronic renal disease. The cause of the abnormal secretion of TSH and PRL in chronic renal failure is discussed in the light of clinical importance.     

Dopamine infusion and anterior pituitary gland function in very low birth weight infants

BACKGROUND: Previous studies demonstrated that dopamine infusion reduces plasma concentration of thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) in adults, children, and infants. OBJECTIVES: The purpose of this prospective observational study was to evaluate the relationship between dopamine infusion and the dynamics of T4, TSH, PRL, and GH in preterm newborns weighing less than 1,500 g (very low birth weight infants, VLBW) admitted in a neonatal intensive care unit of a university hospital over a one year period. METHODS: A total of 97 preterm newborns were enrolled and divided into two groups: group B included hypotensive infants treated with plasma expanders and dopamine infusion; group A was the control group including newborns who were never treated with dopamine. The newborns were studied dynamically through blood samples taken every day till 10 days. Newborns of group B were studied during dopamine infusion and after its withdrawal. RESULTS: Among the VLBW newborns who were given dopamine, the four pituitary hormones had different dynamics: a reduction of T4, TSH, and PRL levels was noticed since the first day of treatment, and a rebound of their levels was evident since the first day after its interruption. On the contrary, the postprandial GH levels were roughly constant: GH plasma concentrations were in fact a little lower in newborns treated with dopamine, and a slight increase was observed after its withdrawal. However, observed differences were not statistically significant. CONCLUSIONS: The results suggest that dopamine infusion reduces T4, TSH, and PRL plasma levels in preterm VLBW infants and have no effect on postprandial GH rate. This hormonal suppression reverses rapidly after dopamine withdrawal. This observation suggests that the iatrogenic pituitary suppression probably cannot produce long-term injuries.     

Prolactin response to thyrotropin-releasing hormone in children with Turner's syndrome and hyperthyroidism

Plasma prolactin (PRL) response to synthetic thyrotropin-releasing hormone (TRH) was studied in 26 prepubertal and 19 pubertal children with constitutional short stature, 7 patients with Turner's syndrome and 10 patients with hyperthyroidism. The mean basal concentrations of plasma PRL did not differ among groups. In prepubertal children PRL responses to TRH were comparable in both sexes, while pubertal children plasma PRL levels after TRH in females were significantly higher (P<0.05) than those in age-matched males. Plasma PRL levels after TRH in patients with Turner's syndrome were significantly higher (P<0.05) than those in age-matched males, but were not significantly different from those in age-matched females. Plasma PRL response to TRH was markedly suppressed in patients with hyperthyroidism before treatment, but it returned to normal after treatment when patients became euthyroid. A significant correlation (P<0.05) between peak concentrations of plasma PRL after TRH stimulation and plasma T₃ but not T₄ levels was observed.These data suggest that a sex difference in TRH-stimulated PRL secretion appears around puberty and that plasma PRL response to TRH is suppressed in children with hyperthyroidism. The magnitude of plasma PRL response to TRH is closely correlated with the severity of hyperthyroidism when judged by plasma T₃ but not T₄ concentrations.     

Multiple associated endocrine abnormalities in a patient with pseudohypoparathyroidism type 1a

A girl with type 1a pseudohypoparathyroidism (PHP) presented several hormonal abnormalities. Although she had eluded neonatal thyroid screening, she was diagnosed as having hypothyroidism at the age of 5 months. Thereafter, a diagnosis of PHP was made on the basis of skeletal features of Albright osteodystrophy and lack of both cyclic adenosine monophosphate (c-AMP) and phosphaturic responses after parathyroid hormone (PTH) infusion. The basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were higher than normal and showed exaggerated responses to luteinizing hormone-releasing hormone (LH-RH). There was no growth hormone (GH) response to arginine infusion, and the prolactin (PRL) response after thyrotropin-releasing hormone (TRH) infusion was also impaired. The stimulating guanine nucleotide-binding protein (Ns) activity of the erythrocytes was reduced to 66.9%. The skeletal age was not delayed at the age of 5 months in spite of the hypothyroid state, and it advanced following thyroxine and vitamin D treatments.Abbreviations PHP pseudohypoparathyroidism - c-AMP cyclic adenosine monophosphate - PTH parathyroid hormone - LH luteinizing hormone - FSH follicle-stimulating hormone - LH-RH luteinizing hormone-releasing hormone - GH growth hormone - PRL prolactin - TRH TSH-releasing hormone - Ns stimulating guanine nucleotide-binding protein - TSH thyroid stimulating hormone - Pi/cr phosphate/creatinine ratio     

急性白血病化疗对垂体、性腺、甲状腺激素的影响

目的评价儿童急性白血病(AL)及联合化疗对其垂体、性腺、甲状腺激素的影响。方法测定37例(男23例,女14例)AL患儿化疗前后和20例对照组血清促卵泡激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)、催乳素(PRL)、生长激素(GH)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平。结果AL患儿FSH、LH、T、E2、GH、FT4、TSH水平化疗前后及对照组各组差异无显著意义(P>0.05),PRL水平治疗前高于对照组(P<0.01),男童PRL水平治疗前后比较差异有显著意义(P<0.01)。FT3治疗前低于对照组(P<0.001),治疗后趋于正常(P>0.05)。结论AL本身及联合化疗对患儿垂体-性腺轴功能及GH水平无明显影响。AL本身可使PRL水平升高,而化疗药物可抑制男童PRL的分泌。联合化疗对甲状腺功能无影响,FT3水平对判断AL患儿病情变化、疗效及预后有一定参考意义。     

Familial growth retardation with isolated thyroid-stimulating hormone deficiency

Three brothers with isolated thyroid-stimulating hormone (TSH) deficiency were observed at ages 17, 15, and 10 years. They suffered from severely retarded growth, with a marked retardation in bone maturation. Their serum T4, T3, and TSH levels were low. Serum thyrotropin-releasing hormone (TRH) concentration was normal. No increases in TSH levels were elicited during the TRH test. The other pituitary hormones, adrenocorticotropic hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin hormone, responded normally to stimulation. Thyroxin treatment triggered a growth acceleration. Genetic investigation revealed several instances of small stature on the father's side.     

Regulation of growth hormone release in fetal calves

Plasma GH and IGF1 concentrations were measured during the last 2 months of gestation in 9 chronically catheterized fetal calves under basal conditions or following growth-hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) or SRIF intravenous cotyledonnary injections. Plasma GH concentrations were higher in fetuses (1.40 +/- 0.10 nmol/l) than in dams (0.14 +/- 0.01 nmol/l). Plasma GH secretory profile was pulsatile. The number of secretory pulses, as well as their magnitude and mean baseline values decreased from 220 to 270 days of gestation. Synthetic 1-29 GRF or TRH increased fetal plasma GH concentration at 250 and 270 days of gestation but was devoid of any significant effect at 220 days. SRIF injection decreased plasma GH concentration in 270-day-old fetuses. Plasma IGF1 concentrations were lower in fetuses than in dams. No treatment had a significant effect on fetal and maternal IGF1 levels.     

Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings

Female patients with anorexia nervosa (a.n.) are characterized by distinct endocrine features probably due to hypothalamic pituitary dysfunctions. There is only a limited number of case reports available on patients with a.n.; mostly with few data on hormones. In six male patients with a.n. we examined basal and stimulation values of several hormones performing three pituitary function tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle stimulating hormone (FSH) after LHRH were low comparable to results in prepuberal boys. Similarly, testosterone levels in serum were also markedly reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in one patient and at the lower limit in two patients; concentration of free T4 was in the normal range, while five of six subjects had reduced total T3 concentration and two of six patients showed increased reversed T3 levels; TBG concentration was always in the normal range. Basal TSH was normal, while in two patients the TSH stimulation levels after TRH were diminished; in all patients the TSH stimulation levels were found to be delayed. The basal levels of growth hormone were normal, but the growth hormone response after insulin was diminished in four patients. In all six patients basal prolactin (PRL) and PRL concentration after TRH stimulation was in the normal range. The neuroendocrine results in the six patients with a.n. confirm in males a similar hypothalamic-pituitary dysfunction as it is already known for female patients.     

Endocrine activity in preterm and full-term lambs. 1. Adrenal response to synacthen. 2. Thyroid response to ovine thyroid-stimulating hormone or thyrotropin-releasing hormone

Neonatal endocrine status was studied in 14 lambs born 7 days before term, after estrogen injection into the ewes, and in 15 full-term animals. Plasma cortisol and triiodothyronine (T3) levels were depressed during the first hours of life in preterm lambs and plasma reverse T3 levels were significantly higher than in controls. The rise in plasma cortisol levels after Synacthen injection was significantly lowered by prematurity, suggesting reduced sensitivity of the adrenal cortex to ACTH. After ovine TSH injection, plasma thyroxine (T4) levels increased during a shorter period of time in preterm lambs, resulting in a lowered T4 rise; the T3 response was not affected by prematurity. After TRH injection, the rises in plasma T3 and T4 levels were significantly higher in preterm than in full-term lambs, suggesting a pituitary hypersensitivity to TRH linked to prematurity. Moreover it appeared that the response of reverse T3 to TSH or TRH was very weak.