Dopamine receptors,controlling dopamine levels in rat adrenal glands — comparison with central dopaminergic autoreceptors

Summary Previous work in this laboratory, as well as observations reported in the literature, indicate that the adrenal medulla contains dopamine (DA) receptors of the D-2 subtype, which among other things are capable of controlling the DA level in rat adrenal glands. To further characterize the DA receptors involved in the control of the adrenal DA level, the effects of 9 DA receptor agonists with various intrinsic activities were compared. After various periods of drug administration the rats were killed by decapitation and the DA content of the adrenal glands and the DOPAC content of the forebrain were measured by high-performance liquid chromatography with electrochemical detection. All the investigated DA receptors agonists caused an increase in adrenal DA level, although statistical significance was not reached in one case /(–)-HW165/. Domperidone, a DA D-2 receptor antagonist which does not readily cross the blood brain barrier, blocked the DA-elevating effects of apomorphine, quinpirole, B-HT 920 and both enantiomers of 3-PPP. For the two ergolines terguride and SDZ 208-920 the blockade by domperidone was not complete, suggesting that their effects are mediated not only through DA, but also through other receptor systems. The dose of domperidone used (3 mg/kg) had but a marginal influence on brain DOPAC levels, supporting the almost exclusively peripheral effect of this agent. Our data indicate that the DA D-2 receptors which control the DA level in the adrenal medulla in rats, have characteristics similar to, though not identical with the autoreceptors in the forebrain.     

附子对大鼠的抗炎作用

本研究结果表明附子煎剂对巴豆油所致小鼠耳部炎症,甲醛所致大鼠脚跖肿胀有显著抑制作用,切除双侧肾上腺的大鼠,附子煎剂对甲醛所致的足跖肿胀仍有明显抑制作用。提示附子具有抗炎症作用,且附子的抗炎症作用与肾上腺系统无明显关系。     

ENDOTHELIN RECEPTORS IN RAT ADRENAL GLAND VISUALIZED BY QUANTITATIVE AUTORADIOGRAPHY

1. The radioligand [125I]-endothelin was used to map receptors for endothelin in rat adrenal gland using in vitro autoradiography and computerized densitometry. 2. In the adrenal, a high density of binding was found in the adrenal medulla (binding affinity constant 0.18 +/- 0.11 X 10(9)M-1) and zona glomerulosa (binding affinity constant 0.18 +/- 0.07 X 10(9)M-1). Binding was low to undetectable in the zona fasciculata and zona reticularis. Unrelated peptides did not displace endothelin. 3. These results provide evidence of endothelin receptor distribution in adrenal gland and suggest that endothelin might exert multiple actions in the adrenal gland on catecholamine and aldosterone biosynthesis and secretion.     

Patterns of angiogenesis in neural transplant models: I. Autonomic tissue transplants

Functional vascular connections must form rapidly to prevent ischemic damage to grafted neural tissues. The temporal sequence by which transplant circulation is re-established provides information about the angiogenic capacity of either intact or damaged CNS blood vessels. This study compares the time course and mechanism of vascular reperfusion in allografts of superior cervical ganglia or adrenal medulla inserted either into the fourth ventricle or directly into the parietal cortex of perinatal rats. Tritiated thymidine was administered to recipients to determine angiogenic patterns at various postoperative time periods. After processing for light microscopic autoradiography, host and graft endothelial labelling indices were determined in order to establish the temporal sequence and location of vascular proliferation. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H thymidine prior to transplantation to determine if host vessels invaded the grafts. Intraventricular graft vessels initially collapsed but sustained minimal ischemic damage and were completely reperfused by 24 hours postoperative. Adjacent intact host vessels attained peak 3H thymidine incorporation at 20 hours. Intrinsic graft vessels were radioactively labelled only after 48 hours. Intraparenchymal transplants surrounded by minimal trauma exhibited a similar temporal sequence of reperfusion and host endothelial proliferation. Intrinsic graft vessels in intraparenchymal grafts sustained more severe damage. With increased trauma, a concomitant delay in graft reperfusion time was observed. Grafts within prelabelled hosts rarely contained any labelled endothelium, indicating that anastomotic connections were made between original, intrinsic graft vessels and nearby host vascular sprouts. This study demonstrates that mature autonomic tissue stimulates the growth of adjacent host vessels when transplanted to undamaged brain surfaces. The anastomosis of nascent host vessels with pre-existing graft vessels is responsible for the rapid re-establishment of circulation within the transplants. A similar mechanism occurs within intraparenchymal grafts, although the rapidity of reperfusion appears to be predicated on the amount of trauma present at the graft site.     

In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated.     

亚临床甲状腺功能减退症患者TSH与肾上腺皮质功能的关系

目的分析亚临床甲状腺功能减退症患者促甲状腺激素(TSH)与肾上腺皮质功能的关系。 方法选取150例亚临床甲状腺功能减退症患者为研究组,甲状腺功能正常的健康人群150例为对照组。比较两组TSH、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、皮质醇(CORT)和促肾上腺皮质激素(ACTH)水平。采用Pearson法分析亚临床甲状腺功能减退症患者TSH水平与ACTH、CORT水平的相关性。 结果与对照组比较,研究组患者TSH、ACTH水平升高,CORT水平降低(P＜0.05)。Pearson分析结果显示,亚临床甲状腺功能减退症患者TSH水平与ACTH水平呈正相关(P＜0.05),与CORT水平呈负相关(P＜0.05)。 结论亚临床甲状腺功能减退症患者血清TSH水平与肾上腺皮质功能指标ACTH、CORT水平存在相关性。     

N-cadherin expression in adrenal tumors: upregulation in malignant pheochromocytoma and downregulation in adrenocortical carcinoma

Cell adhesion molecules (CAMs) are important regulators of tumor growth. The aim of the present study was to evaluate the expression pattern of CAMs in adrenal tumors regarding origin (cortex vs medulla) and biologic behavior (benign vs malignant). Eighty-seven adrenal tumors were investigated by immunocytochemistry (ICC) using monoclonal antibodies against N-cadherin (NCAD), E-cadherin (ECAD), neural cell adhesion molecule (NCAM), and CD44. Western blotting was performed on 30 tumors using the same antibodies. Markers for proliferation (Ki-67) and catecholamine synthesis (tyrosine hydroxylase) were also analyzed in tumors by ICC. NCAD was expressed in 12/27 benign pheochromocytomas (BPCs) (12 familial cases), 8/8 malignant pheochromocytomas (MPCs), 28/30 adrenocortical adenomas, and 9/22 adrenocortical carcinomas. ECAD was expressed in 0/27 BPCs, 0/8 MPCs, 0/30 adrenocortical adenomas, and 2/22 adrenocortical carcinomas. NCAM was expressed in 26/27 BPCs, 7/8 MPCs, 21/30 adrenocrotical adenomas, and 17/22 adrenocortical carcinomas. CD44 was expressed in 23/27 BPCs, 6/8 MPCs, 7/30 adrenocortical adenomas, and 4/22 adrenocortical carcinomas. Both cortical and medullary adrenal tumors expressed NCAD, NCAM, and CD44 but were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of tumors. NCAD was upregulated in MPCs, but downregulated in adrenocortical carcinoma. Thus, NCAD appears to be involved in the development of both cortical and medullary adrenal tumors.     

Endocrinology: Substrate dependency of C19 conjugates in hirsute hyperandrogenic women and the influence of adrenal androgen

Serum C₁₉ conjugates, specifically 3-androstanediol glucuronide(3G), reflect peripheral androgen action through the actionof 5-reductase activity. The origin of 5-reduced C₁₉ conjugateshas been controversial and it has been suggested that they arederived primarily from adrenal androgens. We examined concentrationsof 3G, 3-androstanediol sulphate (3S), androsterone glucuronide(AoG) and androsterone sulphate (AoS) in 40 hirsute hyperandrogenicwomen. These patients were divided into four groups based uponindividual, combined or normal concentrations of the adrenalandrogens dehydroepiandrosterone (DHEAS) and 11-hydroxy-androstenedione.Testosterone, unbound testosterone and androstenedione weresimilar in these groups. Serum 3G was equally high in all groupsand was correlated significantly with hirsutism, while the otherconjugates were not. Androsterone glucuronide was raised inall groups but was higher in patients with raised DHEAS. Serum3S was raised in all groups and was higher where both adrenalandrogens were raised. Serum AoS was highly correlated withDHEAS. Serum 3G was correlated with unbound testosterone andandrostenedione but not with the adrenal androgens. The glucuronideconjugates were correlated with one another as were the sulphateconjugates but glucuronides and sulphates were not correlated.These data confirm ovarian and adrenal dependency of C₁₉ conjugates.Serum 3G appears to reflect hirsutism most accurately and isleast dependent on adrenal androgens in patients with mixedhyperandrogenism.     

Restriction fragment length polymorphisms of the CYP11B1 gene in the Japanese population

Summary Restriction fragment length polymorphisms (RFLPs) of the CYP11B1 gene were studied in Japanese using cDNA clone P450c11 as a probe. Genomic DNAs from 60 unrelated Japanese individuals were digested with 8 different restriction enzymes and analyzed by Southern blot hybridization. Two RFLPs were detected inMspI digests of the DNA. One(A) was characterized by polymorphic bands at 3.4 and 2.5 kilobasepairs (kb) and the other (B) by polymorphic bands at 1.7 and 1.2 kb. The third RFLP was observed inPvuII-digested samples and was polymorphic at 5.8 and 4.0 kb bands. Two of the three RFLPs found, RFLP (A) and (C), have not been described in the only previous report which was based on Caucasian samples. We also examined the RFLPs of a 3 generation family of 11-hydroxylase deficiency caused by an abnormality of the CYP11B1 gene. All the family members were homozygous in all three RFLPs and was thus not informative.     

肾上腺肌纤维母细胞瘤

目的：观察肌纤维母细胞瘤形态及免疫组化特点。方法：对１例儿童肾上腺的肌纤维母细胞瘤进行光镜观察和免疫组化染色。结果：ＨＥ中瘤细胞呈梭形、不规则形，排列无序，间杂以淋巴细胞等浸润及胶原纤维束；免疫组化显示瘤细胞Ｖｉｍ（＋），ＳＭＡ＋（＋），ＣｇＡ（－），ＥＭＡ（－）。手术彻底切除肿瘤后，患者临床症状消失。结论：肌纤维母细胞瘤是由既具有平滑肌细胞特征，又具有纤维母细胞特征的独立性肿瘤。