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 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 growth- hormone stimulating activity) The balance between the effects of these hypothalamic factors on pituitary will determine the level of growth hormone release

Abnormalities of GH – Location of the lesions GH production and receptor binding GH deficiency and excess has a very important role of this hormone in normal physiology Such disorders can result from lesions either in the : Hypothalamus or the pituitary affecting production or 1 Target cells for Receptor binding 2

Deficiency of GH – the types Hereditary or acquired The manifestations of GH deficiency depends upon: The age of the of onset of the disorder or 1 The cause whether it is heritable or acquired disease GH deficiency results Dwarfism in children GH deficiency is rare in adults

Dwarfism – Special features 1 Appropriate proportion of body parts All the physical body parts like size of hands and feet develop in appropriate proportion to each other but 1 The rate of development is greatly reduced, ≥ 4 feet 2 The affected child appears to be younger than his actual age A child at the age of 10 years may have body development of a child aged 4 -5 – years 3

Dwarfism 0r growth retardation in children

GH deficiency in Adults – is rare GH deficiency in adults is rare It results in reduction of muscle mass, visceral fat deposition and osteoporosis Leads to abnormal lipid profile

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 Key factor for the promotion of growth by GH

Treatment Human Growth hormone preparation Human growth hormone synthesized by Escherichia coli bacteria as a result of application of recombinant DNA If Dwarfs have pure deficiency of GH completely cure by HGH

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)

GH excess – Types. 2. (age) In children and adults GH is secreted more than body requirements The effects of GH excess depend on the age of onset, both in children and adults – 2 conditions Giantism or Gigantism : This condition occurs in children when epiphysis are not Fused Acromegaly: when epiphysis are fused in adults

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

GH excess in adults – Acromegaly Acromegaly results from excessive secretion of growth hormone in adults with fused epiphysis It is usually the result of benign pituitary adenoma in middle aged individuals Excessive secretion of GH leads to excessive generation of IGF-1 - the mediator of the effects of GH

Acromegaly – No ↑in height ↑in soft tissue /viscera There is no ↑ in height but soft tissue proliferation Enlargement of bones of hands and feet with swelling Over growth of the Skull, lower jaw and bulging of forehead Prominent nose, thick lips and tongue ↑ in the size of the viscera like Liver and heart

Acromegaly – No ↑in height ↑in soft tissue /viscera There is no ↑ in height but soft tissue proliferation Enlargement of bones of hands and feet with swelling Over growth of the Skull, lower jaw and bulging of forehead Prominent nose, thick lips and tongue ↑ in the size of the viscera like Liver and heart

Acromegaly –↑ in bone thickness and soft tissues

Acromegaly - Wide sole of foot

Acromegaly – Large skull. lower jaw, nose and Bulging Forehea d

GH excess in Children- Giantism when epiphysis are not fused Giantism in children and adolescents occurs when epiphysis are not fused Chronic GH secretion leads to linear growth of long bones usually to 7- 9 feet Hyper secretion of GH is commonly associated with hypogonadism and cause of non fusion of epiphysis

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

Gigantism 7 feet 8 inches Pituitary gland tumor

Treatment Surgical removal of tumor or irradiation

Difference B/W Acromegaly and Giantism