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Pituitary Gland (hypophysis) 1 cm in diameter and 0.5 to 1 gm in weight Lies in sella turcica (bony cavity at the base of brain Connected to hypothalamus by pituitary stalk Physiologically it is divided into two parts Anterior pituitary (adenohypophysis) Posterior pituitary (neurohypophysis) Pars intermedia is small avascular zone between the two. Embryologically the two parts develop from different sources Anterior pituitary from Rathke’s pouch (invagination of pharyngeal epithelium) Posterior pituitary from neural tissue outgrowth from hypothalamus Anterior Pituitary Hormones Cell Types in the Anterior Pituitary Somatotropes (acidophils) (30-40%) Corticotropes (20%) Thyrotropes Gonadotropes Lactotropes Posterior Pituitary Hormones Antidiuretic Hormone Oxytocin These hormones are secreted by magnocellular neurons located in the supraoptic and paraventricular nucleus of hypothalamus Hypothalamus controls pituitary secretion There are neural connections between the hypothalamus and the posterior pituitary and vascular connections between the hypothalamus and anterior pituitary Hypothalamic Releasing and Inhibitory Hormones Thyrotropin-releasing hormone Corticotropin-releasing hormone Growth hormone-releasing hormone Growth hormone-inhibitory hormone Gonadotropin-releasing hormone Prolactin inhibitory hormone These hypothalamic releasing and inhibitory hormones are conducted through minute blood vessels called hypothalamic-hypophysial portal vessels to the anterior pituitary gland The hypothalamic-hypophysial portal vessels form a direct vascular link between hypothalamus and the anterior pituitary Hypothalamic- Hypophysial Portal Blood Vessels Hypothalamic releasing and inhibitory hormones are secreted into median eminence The neurons secreting these factors are present in different parts of hypothalamus Their endings secrete these factors into the tissue fluid from where theses hormones are absorbed into hypothalamic-hypophysial portal system Growth Hormone (somatotropic hormone or somatotropin) Protein hormone (191 amino acids), molecular weight 22,005 Approximately 50% of the circulating pool of growth hormone is in the bound form providing reservoir to prevent fluctuations The half life of circulating growth hormone in humans is 6-20 min and daily growth hormone output is 0.2-1.0 mg/dl The plasma growth hormone level is less than 3 ng/ml Physiological Functions of Growth Hormone Growth hormone promotes growth of almost all the body tissues It promotes increase in size of cells, increased mitosis and differentiation of certain type of cells such as bone growth cells, muscle cells . Effect of Growth hormone on Skeletal frame work Increased deposition of protein by chondrocytic and osteogenic cells Increased rate of reproduction of these cells Conversion of chondrocytes into osteogenic cells causing bone deposition Long bones grow in length at the epiphysial cartilages where epiphysis at the ends of long bones are separated from shaft. Lengthening does not occur if epiphysis are united with the shaft Growth hormone strongly stimulates osteoblasts so bones can become thicker under the influence of growth hormone through out life Growth Hormone is Potent Protein Sparer Growth hormone promotes protein deposition in tissues by increasing amino acid transport through cell membrane Enhancement of mRNA Translation Increased nuclear transcription of DNA to mRNA (over prolonged periods) Decreased catabolism of proteins and amino acids Growth hormone enhances Fat utilization for energy Fats are used for energy in preference to the use of carbohydrates and proteins Release of fatty acids from adipose tissue Conversion of fatty acids to acetyl-CoA Mobilization of fat by growth hormone requires several hours whereas enhancement of protein synthesis can begin in minutes Ketogenic Effect of Excess Growth Hormone The growth hormone increases free fatty acid levels in the blood which are utilized for providing energy. When excess quantities of growth hormone are present large quantities of acetoacetic acid formed by liver are released into body fluids causing Ketosis Growth Hormone Decreases Carbohydrate Utilization Growth hormone increases blood glucose levels Decreased glucose uptake in tissues such as muscle and fat Increased glucose production by the liver Increased Insulin secretion (causes insulin resistance) Growth Hormone Effects are Diabetogenic Growth hormone causes insulin resistance Decreased glucose utilization by the cells Raising blood levels of fatty acids above normal decreases the sensitivity of liver and skeletal muscle to Insulin’s effects Insulin and carbohydrates are necessary for growth hormone to exert its growth promoting action (insulin has also protein anabolic effect) Growth hormone increases the ability of pancreas to respond to insulinogenic stimuli such as glucose Growth Harmone effect on electrolytes Growth hormone increases intestinal absorption of calcium Growth hormone reduces excretion of sodium and potassium Somatomedins(insulin like growth factors) The effects of growth hormone on growth, cartilage and protein metabolism depend on interaction between growth hormone and somatomedins which are polypeptide growth factors secreted by liver and other tissues IGF-I (somatomedin-C) Secretion of IGF-I before birth is independent of growth hormone but is stimulated by growth hormone after birth It has pronounced growth promoting activity Its concentration in plasma rises during childhood, peaks at the time of puberty and declines in the old age. The IGF-I receptor is very similar to Insulin receptor Duration of Action of Somatomedin C Half life of somatomedin C is 20 hrs whereas that of growth hormone is 20 minutes Somatomedin C is strongly attached to plasma protein and released slowly Growth hormone is bound loosely IGF-II IGF-II plays important role in the growth of fetus and its secretion is independent of growth hormone Growth hormone and somatomedins can act both in cooperation and independently to stimulate pathways that lead to growth Diurnal variations in Growth hormone Secretion The levels of Growth hormone are low during the day During sleep large pulsatile bursts of Growth hormone secretion occur (specially in first two hours of deep sleep) Secretion of Growth hormone is under Hypothalamic control Regulation of Growth Hormone Secretion GHRH GHIH (somatostatin) Ghrelin (it is mainly secreted in stomach but also produced in hypothalamus and it has marked growthhormone stimulating activity) The balance between the effects of these hypothalamic factors on pituitary will determine the level of growth hormone release Panhypopituitarism Decreased secretion of all the anterior pituitary hormones. It may be Congenital Acquired (tumor destroying the gland) Dwarfism Causes Panhypopituitarism during childhood All body parts develop in appropriate proportion but the rate of development is slow The child does not pass through puberty If there is only growth hormone deficiency the sexual maturity occurs African pygmy (Levi-Lorain dwarf) Rate of growth hormone secretion is normal or high There is growth hormone insensitivity and there is hereditary inability to form somatomedin C Treatment Human Growth hormone preparation Panhypopituitarsm in Adults Tumors (craniopharyngiomas, chromophobe tumors) Thrombosis of pituitary vessels, infarction of the gland due to shock after delivery in women Effects Hypothyroidism Decreased secretion of adrenal hormones Decreased secretion of gonadotropic hormones (sexual functions are lost) Gigantism Cause Acidophilic tumors of anterior pituitary before puberty All the body tissues grow very rapidly If the condition develops before the union of shaft and epiphysis the person becomes giant There is hyperglycemia Treatment Surgical removal of tumor or irradiation Acromegaly Cause Acidophilic tumor after puberty The bones continue to become thicker Soft tissues also become thicker There is enlargement of viscera specially kidneys, liver, tongue The bone enlargement is specially marked in membranous bones There is kyphosis