THYROID HORMONE, OESTROGEN, AND GLUCOCORTICOID EFFECTS ON TWO DIFFERENT PITUITARY GLYCOPROTEIN HORMONE ALPHA SUBUNIT POOLS

Seven hypothyroid women (six postmenopausal and one premenopausal) were treated with 200 or 300 μg of levo-T4 daily in order to suppress the secretion of TSH and its alpha and beta subunits. After such therapy, serum TSH and beta subunit of TSH (TSH-β) levels were usually not detectable. Serum alpha decreased from a mean value of 4.5 ± 0.8 ng/ml to 2.8 ± 0.4 ng/ml (P > 0.01). Serum LH and FSH levels were unchanged. Oestrogen administration (20 mg diethylstilboestrol daily for 3 or 5 days) to these patients further decreased mean serum alpha to 1.9 ± 0.2 ng/ml (P > 0.005). In addition serum LH, FSH, and the beta subunits of LH and FSH decreased with oestrogen treatment. In separate experiments glucocorticoids (dexamethasone 4 mg every 6 hours for 10 doses) were administered to eight normal individuals, four women with decreased thyroid reserve, and one hyper-thyroid woman. Not only did basal and TRH-stimulated TSH secretion decrease, but secretion of alpha and TSH-β also decreased after dexamethasone administration, with the largest fall in the patients with decreased thyroid reserve. The change in these thirteen patients’ alpha subunit increment after TRH administration was from a mean of 1.6 to 1.0 ng/ml with glucocorticoids; the change in TSH-β was from a mean of 1.1 to 0.7 ng/ml. Serum LH and FSH concentrations were not altered by glucocorticoid administration. These studies have demonstrated two different pools of alpha subunits in the pituitary gland. Thyroid hormone and glucocorticoids decreased secretion of alpha subunits arising from the thyrotroph; oestrogen decreased secretion of alpha subunits arising from the gonadotroph.     

AMIODARONE AND THYROID HORMONE ACTION JAYNE A.

In clinically euthyroid subjects on long-term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.     

PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONE

A 32-year-old Caucasian male, clinically euthyroid, with paranoid schizophrenia and granulocytopenia, had elevated total and free serum T4 and T3; serum TSH was normal (2.7 +/- 0.7 micronU/ml). There was no goitre present, no evidence of Graves' disease, and no evidence of pituitary tumour. He had a normal response to methyl-TRH, with a TSH increment of 14.6 micronU/ml, T3 increment of 212 ng/dl, and T4 increment of 4.7 microgram/dl; baseline value and decreased the TSH increment in response to methyl-TRH. T3 therapy (100 microgram/day) decreased the thyroidal radioactive iodine uptake to less than half the baseline prolactin was normal with a normal response to methyl-TRH to 4.1 micronU/ml. Iodine therapy caused an increase in his baseline TSH with an increase in the TSH response to TSH. The metabolic clearance rates (MCR) and production rates (PR) of T3 and T4 were increased. Baseline serum levels of glycoprotein hormone alpha-subunit were normal and showed a slight increase in response to methyl-TRH, similar to normal subjects. This patient has evidence of partial pituitary and peripheral resistance to thyroid hormone; his only evidence for hyperthyroidism is the elevated MCR and PR of T3 and T4.     

盐负荷及单纯性脱水对心房肽基因表达的影响

大鼠饮0.9%NaCl(盐负荷)或禁水(单纯性脱水)分别持续2、4、6天。冷酚法提取心房中总RNA,用α-~(32)P-标记的大鼠心房肽cDNA探针与之杂交。结果表明。心房肽mRNA长约1000碱基,盐负荷和单纯性脱水显著影响心房肽mRNA的含量。盐负荷组分别为对照组的2.4、2.8和2.0倍;单纯性脱水组分别为对照组的2.1、1.6和0.38倍。盐负荷及禁水时血浆[Na~ ]显著增加。盐负荷时心房肽mRNA含量变化与血浆[Na~ ]平行。结果提示,水盐平衡显著影响心房肽基因表达。     

THE INTERACTION OF GROWTH HORMONE RELEASING HORMONE WITH OTHER HYPOTHALAMIC HORMONES ON THE RELEASE OF ANTERIOR PITUITARY HORMONES

To determine whether the 29 amino-acid fragment of growth hormone releasing hormone (GHRH) can be combined with other hypothalamic releasing hormones in a single test of anterior pituitary reserve, the responses of anterior pituitary hormones to combinations of an i.v. bolus of GHRH(1-29)NH2 or saline with an i.v. bolus of either LH releasing hormone (LHRH) plus TRH, ovine CRH(oCRH) or saline were studied. Each infusion of GHRH(1-29)NH2 resulted in a rapid increment of the plasma GH value. Infusion of GHRH(1-29)NH2 also caused a small and transient rise in plasma PRL, but no change in the integrated PRL response. The combination of GHRH(1-29)NH2 with LHRH plus TRH caused a larger increment of peak and integrated plasma TSH levels than LHRH plus TRH alone. GHRH(1-29)NH2 did not affect the release of other anterior pituitary hormones after infusion with oCRH or LHRH plus TRH. Because of the finding of potentiation of the TSH-releasing activity of LHRH plus TRH by GHRH(1-29)NH2, the study was extended to the investigation of TSH release after infusion of TRH in combination with either GHRH(1-29)NH2 or GHRH(1-40). In this study the combination of TRH with both GHRH preparations also caused a larger increment of the peak and integrated plasma TSH levels than TRH alone. It is concluded that GHRH(1-29)NH2 possesses moderate PRL-releasing activity apart from GH-releasing activity. In addition, GHRH potentiates the TSH-releasing activity of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

FENCLOFENAC-SECONDARY EFFECTS UPON THE PITUITARY THYROID AXIS

To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac therapy, the early period of drug administration was examined in detail and the effect of the drug during a thyrotrophin releasing hormone infusion was assessed. In addition, the effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin-induced hypoglycaemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was found to be insignificant within the therapeutic concentration range of the drug. A sharp, short-lived rise in free thyroxine (21.7 +/- 2.0 to 26.8 +/- 1.9 pmol/l; P less than 0.03) was observed 60 min after the first dose of fenclofenac. Repeated peaks of free thyroxine during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum thyroxine, are postulated to cause the observed suppression of TSH release which is present only until free and total serum thyroxine levels reach their nadir. The time course of the changes seen during thyrotrophin releasing hormone infusion suggested that the pituitary suppression was secondary to a rise in free thyroxine. The responses to hypoglycaemia of those pituitary hormones examined were not affected by fenclofenac.     

促甲状腺激素受体、甲状腺过氧化物酶及甲状腺球蛋白基因表达与自身免疫甲状腺疾病

为探讨促甲状腺激素（ＴＳＨ）受体、甲状腺过氧化物酶（ＴＰＯ）及甲状腺球蛋白（ＴＧ）ｍＲＮＡ在自身免疫甲状腺疾病（ＡＩＴＤ）病人甲状腺组织的表达情况及其相互关系，应用Ｎｏｒｔｈｅｒｎ印记杂交技术观察了ＴＳＨ受体、ＴＰＯ以及ＴＧｍＲＮＡ在７例Ｇｒａｖｅｓ病（ＧＤ），２例桥本甲状腺炎（ＨＴ）病人甲状腺组织中的表达。研究显示：ＴＳＨ受体ｍＲＮＡ与ＴＰＯ和ＴＧｍＲＮＡ在ＧＤ组和ＨＴ组表达不一致，ＧＤ组ＴＳＨ受体ｍＲＮＡ与ＴＰＯ和ＴＧｍＲＮＡ表达基本平行，均有明显增高，ＨＴ组中ＴＳＨ受体ｍＲＮＡ表达与对照组差别不大，但ＴＰＯ、ＴＧｍＲＮＡ表达较低。这种基因表达差异的原因可能与自身免疫性抗体的种类不同、滴度不一致有关。     

FAILURE OF BOMBESIN TO ALTER ANTERIOR PITUITARY HORMONE SECRETION IN MAN

Because of the stimulating effects of bombesin on growth hormone and prolactin secretion in the rat, we have studied the effects of bombesin infusions on anterior pituitary hormone secretion in man. Biological activity of the infused bombesin was confirmed by observing a brisk increase in serum gastrin concentrations and in gastric acid secretion during the lowest dose of bombesin infused. We could demonstrate no effect of bombesin in doses from 200 to 600 pmol.kg⁻¹.h⁻¹ on growth hormone, prolactin, thyrotrophin, luteinizing hormone and follicle stimulating hormone.     

EFFECTS OF CIMETIDINE ON PITUITARY FUNCTION: ALTERATIONS IN HORMONE SECRETION PROFILES

Cimetidine, an H₂ receptor antagonist, was given for 6 weeks to six normal male volunteers to study the effects on pituitary, adrenal, thyroid, and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg four times daily) therapy, and four of the six were restudied after discontinuing cimetidine for 1 month (day 72). Basal TSH concentrations and responses to TRH administration as well as T3 RIA and T4 resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0·15 u/kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (P < 0·01). Response of GH to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P < 0·025) on cimetidine, and returned to baseline on day 72. The 24-h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P < 0·01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P < 0·01) while pulse frequency increased modestly on day 72 (P < 0·05). Peak LH responses to gonadotropin-releasing hormone were also reduced on cimetidine therapy (P < 0·02). Plasma testosterone concentrations did not change but plasma oestradiol concentrations were 38% lower (P < 0·025) after cimetidine was discontinued. H₂ histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.     

EFFECT OF FENOLDOPAM, A DOPAMINE D-1 RECEPTOR AGONIST, ON PITUITARY, GONADAL AND THYROID HORMONE SECRETION

The influence of fenoldopam, a dopamine (DA) D-1 receptor agonist, on basal and GnRH/TRH stimulated PRL, GH, LH, TSH, testosterone and thyroid hormone secretion was studied in nine normal men. All men received 4-h infusions of either 0.9% saline or fenoldopam at an infusion rate of 0.5 microgram/kg min, 12-16 ml/h, adjusted according to weight. After 3 h of infusion, 50 micrograms GnRH and 100 micrograms TRH was given i.v. Blood samples were collected every 15 min from 1 h before to 1 h after the infusion for a total of 6 h for measurements of PRL, LH, FSH, GH, TSH, testosterone, T4 and T3. The median PRL concentration increased significantly (P less than 0.01) to 128%, range 87-287, of preinfusion levels, compared to the decline during control infusion (85%, 78-114). Basal TSH levels declined significantly to 71% (60-91) during fenoldopam compared with 82% (65-115) during control infusion (P less than 0.05). Basal LH, FSH, GH and thyroid hormones were similar during fenoldopam and control infusions (P greater than 0.05). The LH response to GnRH/TRH was significantly (P less than 0.02) increased by fenoldopam infusion. Basal and stimulated testosterone concentration was lower during fenoldopam (P less than 0.01) infusion compared with control. Other hormones were similar after GnRH/TRH stimulation during fenoldopam and saline infusions. These results suggest that DA D-1 receptors are involved in the modulation of pituitary hormone secretion. We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level. Regarding the effect on LH concentrations, an additional direct effect of fenoldopam on testosterone regulation can not be excluded.     

INTERACTION OF THYROTROPHIN RELEASING HORMONE AND THE ENKEPHALIN ANALOGUE DAMME ON PITUITARY HORMONE SECRETION

Because TRH counteracts the inhibitory effect of opiate peptides on LH secretion in cultured cells from normal pituitaries, six normal postmenopausal women were studied to determine whether TRH interacts in vivo with opioid peptides in the regulation of pituitary hormone secretion. At two different times a constant 3 h infusion of either saline or TRH (5 micrograms/min) was initiated. At 60 min a 250 micrograms bolus of the opiate agonist peptide D-Ala2-MePhe4-met-enkephalin-0-ol (DAMME) was injected in one of the two saline and TRH infusion tests. The four treatments, i.e. saline infusion alone, saline infusion with a DAMME bolus, TRH infusion alone; and TRH infusion with DAMME bolus were given at random with an interval of at least 7 d. Blood samples were taken every 15 min during the 3 h study. DAMME induced a significant fall (P less than 0.05) in serum LH (from 35 +/- 8.5 to 18.3 +/- 5.1 mIU/ml) (mean +/- SEM) without significantly affecting FSH levels (from 29 +/- 11.2 to 26.9 +/- 12.4 mIU/ml). These changes were not antagonized by the continuous infusion of TRH. PRL had a monophasic response pattern to continuous isolated TRH infusion; the basal levels increased from 4.2 +/- 1.2 to 24.5 +/- 6.8 ng/ml at 30 min and then slowly decreased with a plateau from 90 min until the end of the study. DAMME administration at 60 min induced a significant second peak of PRL secretion (44 +/- 6.5 ng/ml) 30 min later (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.     

选择性垂体甲状腺激素抵抗所致TSH甲亢一例的治疗观察

本文报告１例选择性垂体对甲状腺激素抵抗所致ＴＳＨ甲亢。用ＰＴＵ治疗１３个月后，血清ＦＴ＿３、ＦＴ＿４水平持续高于正常，血清ＴＳＨ值波动于２６～６０ｍＵ／Ｌ之间，ＴＲＨ兴奋试验呈过度反应。改用溴隐亭治疗６个月后，血清基础ＴＳＨ及ＴＳＨ对ＴＲＨ反应均恢复正常，血清ＴＴ＿３、ＴＴ＿４水平也随之逐渐下降至正常，甲亢症状控制。Ｄ－Ｔ＿４治疗１１天，血清基础ＴＳＨ值保持正常，对ＴＲＨ无反应，而血清ＦＴ＿４、ＴＴ＿４水平回升至高于正常范围，甲亢复发。我们的观察说明，溴隐亭治疗这类甲亢有效，副作用小，可长期使用。     

COMPARATIVE EFFECTS OF SODIUM IPODATE AND IODIDE ON SERUM THYROID HORMONE CONCENTRATIONS IN PATIENTS WITH GRAVES'' DISEASE

Patients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X-ray contrast agent which impairs outer ring (5'-) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14.7 +/- 1.3 microgram/dl (mean +/- SE) to a nadir of 7.9 +/- 0.9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 +/- 43 ng/dl to a nadir of 143 +/- 20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15.1 +/- 0.7 micrograms/dl to a nadir on day 9 of 11.3 +/- 1.0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in ther serum T3 concentration from 340 +/- 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 +/- 15 ng/dl to a peak value of 376 +/- 59 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)     

流行性出血热下丘脑-垂体、甲状腺、肾上腺皮质功能的变化及其意义

对229例EHF患者进行了下丘脑-垂体、甲状腺和肾上腺皮质功能的研究,发现血清PRL、GH、TSH以及血浆F在病程早期和极期有不同程度的增高倾向,多尿期以后逐渐恢复正常。垂体功能试验表明下丘脑-垂体-肾上腺皮质轴及PRL分泌细胞储备功能基本正常,重型和危重型病例血清TT_3下降而rT_3升高,可能是肝、肾功能受损使血清T_4代谢障碍的结果。适当使用免疫调节剂、胰岛素并及时调正内环境可能对患者有利。     

VASOACTIVE INTESTINAL PEPTIDE AND ANTERIOR PITUITARY FUNCTION

Vasoactive intestinal peptide (VIP) is a highly basic 28 amino-acid peptide which was first isolated from porcine small intestine (Said & Mutt, 1970). It is related to several other peptides including PHI (peptide with N-terminal histidine and C-terminal isoleucine amide), secretin, glucagon, and has some sequences similar to those of growth hormone releasing hormone (Fig. 1). The amino-acid sequence of human VIP is identical with that of the porcine form (Itoh et al., 1983). It has been shown that human VIP is cosynthesized with PHM (peptide with N-terminal histidine and C-terminal methionine amide, the human analogue of PHI) from the same large precursor protein (Itoh et al., 1983).     

PITUITARY AND THYROID INSUFFICIENCY IN THALASSAEMIC HAEMOSIDEROSIS

Thyroid and pituitary function tests using hypothalamic releasing factors were performed in seven patients with thalassaemia and secondary haemosiderosis and in a control group of seven healthy subjects. The TSH level in the thalassaemic patients (18.07 +/- 1.10 microU/ml) was higher than in the controls (1.01 +/- 0.14 microU/ml, P less than 0.001). After TRH administration the TSH values increased less than in controls. Serum thyroxine and FT41 values were lower in the group of patients with thalassaemia (76.7 +/- 7.8 nmol/l and 19.3 +/- 2.2) compared to the controls (116.1 +/- 6.9 nmol/l, P less than 0.005 and 38.6 +/- 3.6, P less than 0.001). The basal prolactin values did not differ significantly between the two groups, but after TRH administration the increment was significantly lower in thalassaemics than in controls (P less than 0.005). The basal LH values were lower in the thalassaemic patients (1.37 +/- 0.24 ng/ml) than in the controls (3.23 +/- 0.50 ng/ml) and did not increase significantly after LHRH administration. The FSH values were also lower in the thalassaemic group (0.46 +/- 0.15 ng/ml) compared to the controls (2.06 +/- 0.08 ng/ml, P less than 0.001), and increased only slightly after LHRH administration. We conclude that in thalassaemia pituitary deficiency exists, mostly of gonadotrophs, but possibly also for the thyrotrophs and the lactotrophs. Latent primary hypothyroidism has also been found in the thalassaemic group. The functional abnormalities found in both endocrine glands are best explained as a consequence of coexisting haemosiderosis.