Download 内分泌学―――Lecture Note

内分泌系统——下丘脑与垂体
1. 内分泌系统的主要组成、特征
Hypothalamus and pituitary are anatomically connected by neuro-hypophyseal stalk.
Hypothalamus-pituitary unit forms the most complex and the most dominant component of entire
endocrine system.
2. 内分泌系统和神经系统的比较
Nervous system performs short term crisis management;
Endocrine system regulates long term ongoing metabolic;
Endocrine communication is carried out by endocrine cells releasing hormones:
- Alter metabolic activities of tissues and organs
- Target cells
Paracrine communication involves chemical messengers between cells within one tissue
3. 下丘脑的主要功能：
homeostatic mechanisms:
regulation of body temperature, water balance, and energy production, etc.;
regulation of the behavioral drives of thirst, hunger, and sexual behavior, etc..
4. 神经内分泌概念
5. 下丘脑—垂体门脉系统：
1) Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from
hypothalamus.
2) Hypothalamus is the highest integrative center in the endocrine hierarchy. The secretion of
hypothalamic hormones is pulsatile which is critical for maintaining normal secretion of pituitary.
3) Secretion from the posterior pituitary is controlled by nervous signals that originate in the
hypothalamus and terminate in the posterior pituitary.
4) Secretion by the anterior pituitary is controlled by hormones called hypothalamic
releasing/inhibitory hormones (or factors). These factors are secreted into the interstitial fluid in
median eminence of hypothalamus and absorbed into the capillaries, which is then conducted to
the anterior pituitary through the hypothalamic-hypophyseal portal vessels. In the anterior pituitary,
the hypothalamic releasing or inhibitory hormones act on the endocrine cells to control their
secretion.
6. 下丘脑释放/抑制激素及其垂体靶标:
For most of the anterior pituitary hormones, the releasing hormones are important, but for
prolactin, PIH exerts the most control
7. 下丘脑—垂体——靶腺轴:
1) Hypothalamus regulates pituitary secretion; then pituitary regulates the peripheral glands
secretion. This is known as hypothalamic-pituitary-peripheral gland axis.
2) Although the plasma concentration of many hormones fluctuates in response to various
stimulations that occur throughout the day, all hormones are nicely and closely controlled. In most
instances, this control is achieved through negative feedback mechanisms.
3) Hypothalamus increases pituitary hormone secretion which increases target glands secretion.
Increased peripheral hormone causes feedback control on both hypothalamus and pituitary. This
mechanism is known as long-loop feedback.
4) Pituitary hormone can also effect secretion of related hypothalamic hormone. This is known as
short-loop feedback.
5) Hypothalamic releasing hormone inhibits its own synthesis. This is called ultra-shortloop
feedback.
8. 垂体特征:
• 1 cm diameter, 0.5-1 g
• Lies in sella turcica and is connected to hypothalamus by pituitary stalk
• Two distinct parts – Anterior & Posterior lobes
• Anterior pituitary originates from epithelium; posterior pituitary from neural tissue
• Anterior pituitary secretes six important hormones
• Posterior pituitary secretes two important hormones
9. 垂体前叶分泌的激素、作用靶点、下丘脑对其调节:
10. 生长激素
A. 化学特征:
• GH is also named somatotropin, circulating in two forms (22-kDa & 20-kDa) that have similar
biologic activities
• GH is produced by acidophilic cells of anterior pituitary
• GH is secreted in pulsatile fashion
• GH promotes growth of body tissues by increasing the size & numbers of cells
• Homologous with prolactin and human placenta lactogen (hPL)
B. GH 分泌特征:
1. Daily variation (diurnal pattern) of secretion: the most consistent period for secretion in both
children and adults occurs about one hour after the onset of deep sleep. It is estimated that 70-90%
of the total 24 hours secretion of GH occurs during sleep. The initial surge of GH secretion is
correlated with the onset of stage III and IV sleep. During the day, the secretion of GH is episodic.
2. GH production is slightly increased in children, rises further during puberty then declines to
adult levels, and then further reduction occurs with aging. The declined GH secretion may be
partly responsible for decline in lean body mass, protein synthesis and metabolic rate, as well as
the increase in adipose mass that characterizes elderly humans.
C. GH 代谢:
• Anabolic
- increase amino acid uptake, protein, RNA/DNA synthesis
- decrease amino acid/protein degradation
• Ketogenic
- increase lipolysis
- increase fatty acid oxidation � ketones
• Diabetogenic
- increase plasma glucose (decrease uptake & increase gluconeogenesis)
- increase insulin secretion
D. GH 功能:
• The most striking and specific effect of GH is stimulating growth
• All aspects of the metabolism of chondrocytes (cartilage cells) are stimulated:
- increases RNA, DNA and protein synthesis
- increases proliferation of chondrocytes
- converts prechondrocytes into chondrocytes
- increase collagen formation
• Also stimulates growth of visceral organs
E. GH 和其他促生长激素:
• Optimal growth is not determined by GH only. It is determined by genetics, hormones and
optimal nutrition. Multi-factors contribute to normal growth.
• Within 9 months before being born, the fetus goes from a single cell to a fully developed baby.
Except having enough nutrition, the hormones including insulin, insulin-like growth factor 2
(IGF-II) and hPL are also important.
• After birth, there are several hormones that interplay to regulate growth, including GH, thyroid
hormone, IGF-I, cortisol, insulin, and the sex hormones.
• After birth, growth velocity is initially high, and then decreases. During pubertal development,
velocity increases to its highest level, only to terminate with the closure of the epiphyseal plates
(genetic limits).
• During pubertal development, GH, either directly or indirectly through IGF-I, collaborates with
thyroid hormones, insulin, gonadal hormones and cortisol (permissive effect), to maximize growth
potentia. The contribution of each hormone will be discussed in subsequent lectures.
F. GH and 生长调节素 (胰岛素样生长因子，IGF):
• The growth-promoting effects of GH are mediated by somatomedins
• The effects of somatomedin on growth are similar to the effects of insulin on growth, therefore
they are called Insulin-like growth factor (IGF)
• IGF-I and IGF-II are produced in many tissues, have autocrine, paracrine, and endocrine actions
• The major source of circulating IGF-I is hepatic in origin
• IGF-I synthesis is GH dependent, IGF-II synthesis is less GH dependent
• Fasting and insulin deficiency lead to diminished liver production of IGFs despite increases in
GH secretion
G. IGF 结合蛋白:
• 40% of GH circulates bound to growth hormone binding proteins (GHBP), more than 90% of
IGF-I circulates bound to IGF binding proteins (IGFBP)
• IGFs are more stable than GH in plasma
• Half-life: IGF-I (20 hours), GH (20 minutes)
• Plasma IGF-I level is a valuable measurement of GH secretion
• IGF binding proteins (IGFBP1-6)
- Transport IGFs
- Serve as a large reservoir
- Prevent degradation of IGFs
H. IGF 受体:
• Receptor of IGF-I is a dimer, structurally similar to the insulin receptor and has intrinsic tyrosine
kinase activity
• The receptor of IGF-II is a monomer
• IGFs and insulin cross-react with each other’s receptor, although with lower affinities
M. 控制 GH 分泌的因素:
1. Acute fall of glucose or FFA increases GH secretion. Conversely, high-carb meal causes a
prompt decrease in GH secretion. GH secretion responses to similar changes in FFA level are
slower and smaller.
2. A high protein meal or infusion of mixture of amino acids raises GH level. Arginine is the most
consistent amino acids stimulator. However, the prolonged protein calorie deprivation or total
fasting also stimulates GH secretion, by decreasing negative feedback from peripheral product of
GH action.
3. Exercise and various stresses are rapid stimulators of GH secretion.
4. A regular nocturnal GH peak occurs 1 hour after the onset of deep stage 3 or 4 sleep.
Somatotroph responsiveness to GHRH is increased by sleep.
5. The neurotransmitters dopamine, norepinephrine, acetylcholine, and serotonin all increase GH
secretion by stimulating release of GHRH. The GH responses to exercise, stress, hypoglycemia,
and arginine administration are augmented by α-adrenergic stimulation and are reduced by
β-adrenergic stimulation of receptors in GHRH and somatostatin releasing neurons.
6. Both estrogen and testosterone increase GH secretion but the effect of estrogen is stronger than
testosterone.
7. Although basal cortisol levels stimulate GH gene expression, excess in cortisol decreases GH
responses to GHRH.
8. A decline in pituitary GH occurs during the latter part of pregnancy, perhaps in response to
production of hPL.
9. Obese individuals exhibit dampened GH responses to all stimuli, including GHRH itself.
11. Pro-opiomelanocortin:
• POMC is a precursor hormone from corticotrophs in anterior pituitary
• It is also synthesized by other tissues, e.g. placenta, GI
• POMC is a precursor for:
- ACTH
- β-lipotropin (β-LPH)
- N-terminal peptide
- Melanocyte-stimulating hormone (MSH)
12. 垂体后叶(神经垂体):
• Posterior pituitary is comprised of glial-like cells called pituicytes.
• These pituicytes do not secrete hormones.
• They provide structural support for terminal nerve fibers and endings from hypothalamus.
13. 垂体后叶激素:
1) Posterior pituitary hormones are synthesized by cell bodies in hypothalamus and transported
through the pituitary stalk to posterior pituitary in axoplasm of neuron’s fibers.
2) These nerve endings contain many secretory granules and they lie on the surface of capillaries.
3) These nerve endings release two posterior hormones:
- ADH (vasopressin) is formed primarily from supraoptic nuclei
- Oxytocin is formed primarily from paraventricular nuclei.
14. ADH and oxytocin 的化学特征:
1) Both of these hormones are polypeptide, each contain 9 amino acids. These two hormones are
almost identical except that in ADH, phenylalanine and arginine replace isoleucine and leucine of
the oxytocin molecule. The similarity of the molecule explains their partial functional similarities.
2) The action of ADH includes water retention (antidiuretic hormone – ADH) and increase in
vascular tone (vasopressin).
15. ADH 调节渗透压和细胞外液含量:
1) Osmoreceptor-ADH feedback mechanism regulates ECF osmolarity
2) ADH release is also controlled by cardiovascular reflexes in response to blood volume/pressure
changes
3) Same area that promotes ADH release also stimulates thirst; the two mechanisms work in
parallel.
16. 催产素的功能:
• Contraction of the uterus
- mediates labor contraction
- reduces postpartum bleeding
• Contraction of myoepithelial cells in the breast
- stimulates milk “let-down”