第十二章 内分泌系统
2011-06-08 18:29:38   来源：   作者：  评论：0 点击：

第七节 褪黑素与前列腺素
(Melatonin and Prostaglandin)
一、褪黑素
(Melatonin)
1917年观察到青蛙进食牛松果腺后皮肤变白。五十多年后，Lerne等成功地提取分离出这种物质，命名为褪黑素(melatonin，MLT)。MLT的化学结构为5-甲氧基-N-乙酰色胺，是由松果腺内色氨酸经羟化酶及脱羧酶催化，形成5-羟色胺(5-HT)，然后再经乙酰化和甲基化而生成。
MLT的合成与分泌呈现出明显的昼低夜高的日节律性变化。实验证实持续光照可造成大鼠松果体重量减轻，细胞缩小，MLT合成减少；相反，持续生活在黑暗环境中的大鼠，MLT的合成增加。分别摘除动物眼球、切除支配松果腺的交感神经或损毁动物的视交叉上核后，则MLT分泌的昼夜交替节律消失。因此认为视交叉上核是控制MLT昼夜节律分泌的中枢，交感神经肾上腺素能神经纤维是实现光-暗影响MLT分泌的中介物。
MLT具有广泛的生理功能。近年来研究发现MLT的作用包括：①抑制下丘脑-腺垂体-性腺轴和下丘脑-腺垂体-甲状腺轴的活动 摘除大鼠松果腺后，性腺的重量增加，甲状腺明显增大，碘的更新率加快；②抗衰老作用 大量实验揭示衰老的动物MLT水平下降，给予外源性MLT延缓衰老。研究发现MLT可通过清除体内自由基，调节机体的免疫功能而延缓衰老，MLT能促进IL-2的合成并提高T细胞活性而增强免疫功能；③调整生物节律 人体许多生理功能都呈日周期生物节律，体内各种不同细胞都有各自的日周期节律。下丘脑的视交叉上核可能是生物节律控制中心（生物钟），它使各种位相不同的生物节律统一起来，趋于同步化。而MLT则作为生物节律同步的内源性因子，可使环境周期与生物体的内源节律保持同步。实验证明外源性MLT可使功能紊乱的生物钟，如"时差"得以恢复或重建，也可改善衰老时生物钟不同步等障碍。在下丘脑视交叉上核也发现有大量MLT受体，这为外源性MLT可改善生物钟障碍提供了实验依据；④镇静、催眠、镇痛、抗惊厥及抗抑郁等作用。另外，MLT对心血管、肾、肺、消化系统等均有作用。
二、前列腺素
(Prostaglandin)
前列腺素(prostaglandin，PG)是广泛存在于动物和人体内的一族重要激素，几乎机体所有组织都可合成PG。但因其最初在精液中发现，并首先由前列腺提取，故名前列腺素。PG是含有20个碳原子的不饱和脂肪酸衍生物，其基本结构是前列腺烷酸(prostanotic acid)，具有一个五元环和两条脂肪酸侧链结构。按五环结构不同，把PG分为A、B、C、D、E、F、G、H、I等9种类型。现发现除PGA2和PGI2可在循环系统以激素形式发挥作用外，多数类型的PG只能在组织局部产生释放，调节局部组织的功能，因此被视为组织激素。
PG可分别通过G-蛋白耦联膜受体，经PKA、PLC或Ca2+信号转导途径，以及核受体调控基因转录机制而实现其作用。PG的生物效应广泛而复杂，不同类型的PG作用极不相同，大概总结PG对机体各组织器官的主要作用于表12-7。
表12- 7 前列腺素对机体各系统的主要作用
组织系统 PG的类型 主要作用
心血管系统 PGE、PGF和PGA 正性变时，正性变力
PGI2 扩张冠脉血管，增加冠脉血流量
血液系统 PGI2 抑制血小板聚集和减少血栓形成
呼吸系统 PGE 扩张肺血管，增加肺血流量；松弛支气管平滑肌，降低肺通气阻力
PGF2a 收缩肺血管和支气管平滑肌
消化系统 PGE2、PGI2 抑制胃酸分泌，保护胃粘膜，防止胃粘膜损伤
泌尿系统 PGE2 增加肾血流量，排Na+ 利尿；
PGI2 刺激肾素分泌，增加血管紧张素的合成
生殖系统 PGE 可能与射精和精子运行有重要关系
PGE2、PGF2a 促进排卵、黄体形成、兴奋妊娠子宫等
内分泌系统 PG 促进皮质醇分泌，增加组织对激素的反应性，参与神经内分泌调节
免疫系统 PGE 参与炎性反应，如水肿、疼痛的发生；抑制细胞免疫
Summary
The endocrine system, like the nervous system, adjusts and correlates the activities of the various body systems. Endocrine integration is brought about by hormones. Hormones are chemical messengers produced by endocrine glands and endocrine cells in the organs and tissues of the body. Some of the hormones are amines, and others are amino acids, polypeptides, proteins or steroids. In general, the hormones regulate the processes of metabolism, growth and development, water and electrolyte, reproduction and behavior. The principal mechanisms by which hormones exert their intracellular effects are signal transduction pathways initiated by receptors. There are two very important pathways by which a large share of the hormones function: (1) by activating the second messenger (cAMP, IP3, DAG, and Ca2+ ) via G-proteins for the membrane receptors, hormones, first messengers; or (2) by activating the gene transcription in the cell for the intracellular receptors. Hormone secretion is periodic variations that are controlled by negative and positive feedback mechanisms that ensure a proper level activity of hormone at the target tissue. The major endocrine glands and their hormones are discussed in this chapter:
The both of pituitary and hypothalamus are an anatomy and functional unit. Six very important hormones are secreted by the anterior pituitary, which play major roles in the control of metabolic functions throughout the body, thus: (1) GH promotes growth of the entire body by enhancing protein formation, cell multiplication and differentiation; (2) ACTH controls the section of some of adrenocortical hormones; (3) TSH causes the thyroid gland to secrete T3 and T4; (4) PRL stimulates development of breasts and secretion of milk; (5) FSH and LH control growth of the gonads as well as their hormonal and reproduction. Secretion by the anterior pituitary is controlled by the hypothalamic releasing and inhibitory hormones secreted within the hypothalamus, such as, TRH causes release of TSH; CRH, ACTH; GHRH, GH; GHIH inhibits release of GH; GnRH causes release of LH and FSH; PIF and PRF causes inhibition and release of PRL respectively. ADH and OXT are secreted by the posterior pituitary. ADH promotes water retention. OXT helps milk ejection and contraction of pregnant uterus. The posterior pituitary is controlled by nerve signals that originate in the hypothalamus.
The thyroid secretes large amounts of two hormones, T4 and T3. It also secretes calcitonin. T4 and T3 are synthesized in the colloid by iodination and condensation of tyrosine molecules bound in peptide linkage in thyroglobulin. Physiologic effects of thyroid hormones are increasing the O2 consumption by metabolically active tissues, stimulating lipolysis and protein breakdown, increasing carbohydrate absorption, promoting bone normal growth and brain development, and having chronotropic and inotropic action on the heart, and son on. The absence of thyroid hormones causes mental and physical slowing, poor resistance to cold, and in children, mental retardation and dwarfism. The rate of thyroid secretion is regulated primarily by specific feedback mechanisms, which operate through the hypothalamus (TRH) and anterior pituitary (TSH) to thyroid. The transient inhibition of thyroid hormone synthesis is also caused by the Wolff-Chaikoff effect.
There are two endocrine organs in the adrenal gland. The main secretions of the adrenal medulla are the catecholamines：epinephrine, norepinephrine and dopamine; the adrenal cortex mainly secretes glucocorticoids cortisol, mineralocorticoie aldosterone and sex hormones. Functions of cortical are (1) elevated blood glucose concentration by stimulation of gluconegenesis and decreased glucose utilization in the cell; (2) reduction in cellular protein by decreased protein synthesis and increased catabolism of protein; (3) increased oxidation and use of fatty acids, and develop a peculiar obesity; (4) Resisting stress and blocking the inflammatory response; (5) Decreases the number of eosinophils and lymphocytes, and increase the production of red blood cells; (6) Permissive action for glucagon and catecholamine to exert their effects. Both basal secretion of glucocorticoids and the increased secretion provoked by stress are dependent upon the feedback control of hypothalamus (CRH)-anterior pituitary (ACTH)-adrenal cortex system. Effects of epinephrine and norepinephrine are (1) mimicking the effects of noradrenergic nervous discharge; (2) exerting metabolic effects that include glycogenolysis in liver and skeletal muscle, mobilization of FFA and stimulation of the metabolic rate, and (3) being responsible for the "emergency function of the sympathoadrenal system".
The human pancreas has islets at which secrete insulin and glucagons. Insulin is a small protein synthesized in the beta cells of inlets. The insulin decreases glucose in the blood by preventing breakdown of the glycogen, promoting glycogen synthesis, inhibiting gluconeogenesis, increases the utilization of glucose by the body's tissues; Insulin also promotes fat and protein synthesis and storage. The factors stimulating insulin secretion are increased blood glucose, free fatty acids and amino acids, gastrointestinal hormones, glucagon, GH, cortisol, parasympathetic stimulation, and obesity; The inhibiting factor for insulin secretion are decreased blood glucose, fasting, somatostatin. Human glucagon is produced in a cells of the pancreatic islets when the blood glucose concentration falls. Its functions are opposed to those of insulin. Most important of these functions is to increase the blood glucose concentration by glycogenolysis and glyconeogenesis. Glucagon also increases ketone body formation and stimulates the secretion of GH, insulin, and pancreatic somatostatin. The factors stimulating glucagon secretion are amino acids, CCK, gastrin, cortisol, exercise, infection, and stresses; Inhibiting factors have glucose, Somatostatin, Secretin, FFA, ketones and insulin, and GABA and so on.
Parathyroid hormone (PTH), 1,25-(OH)2-D3, and calcitonin (CT) primarily are concerned with the regulation of calcium metabolism of the body. PTH is secreted by the parathyroid glands. The action of PTH is to increase the plasma Ca2+ and depressing the plasma phosphate by mobilized Ca2+ from bone, increased urinary phosphate excretion, promoted the formation of 1,25-(OH)2-D3, and Ca2+ absorption from the intestine. The secretion of PTH is inhibited by Circulating Ca2+ and 1,25-(OH)2-D3,. Increased plasma phosphate stimulates PTH secretion by lowering plasma Ca2+. 1,25-(OH)2-D3 is formed in the kidneys. Its actions are to increase Ca2+ absorption from the intestine and Ca2+ reabsorption in the kidneys, and to mobilize Ca2+ and PO43- by increasing the number of mature osteoclasts. Formation of 1,25-(OH)2-D3 is regulated in a feedback fashion by plasma Ca2+ and PO43-, and facilitated by PTH, GH and CT. CT secreted by thyroid gland lowers the circulating calcium and phosphate levels by inhibiting bone Ca2+ absorption and increased uric Ca2+ excretion. Plasma CT is directly proportionate to plasma Ca2+, gastrin, CCK, glucagon, and secretin.
The pineal gland secretes melatonin that has function as a timing device to control circadian rhythm. Prostaglandin has been found in many tissues of the body, in addition to the prostate, and affects widespread physiological effects.