Classical & Nonclassical Endocrinology, Pituitary and Hypothalamus CLASS: II M.Sc., UNIT: 1 Prepared By: A. Benno Susai

Introduction These are synthesized at multiple sites and act locally. By contradiction these hormones are Growth factors. But many of these hormones exert opposite activities. Such as growth promotion and inhibition.

Growth Factors (GF) Most GF act in G1 to speed the advance of an already actively dividing cell toward S stage, but have no effect on nondividing cells. These factors are known as Hormones of Progression. Other GF can make nondividing cells sensitive to the hormone of progression, although they themselves cannot actually initiate cell division. These factors are called Hormones of Competency

General Growth Factors Epidermal Growth Factor Family (EGF) Consists of EGF Transforming Growth Factor α (TGF α) Epiregulin Amphiregulin Heparin Binding EGF Cripto-1

Betacellulin Schwannoma Derived EGF (Acetylcholine receptor inducing activity) ARIA Neuregulins Heregulin (Neu differentiation Factor) Glial derived GF Sensory and Motor neuron derived growth factor Both EGF and TGF α are membrane bound precursors (Active) that are cleaved to yield suitable hormones.

The Endocrine System

Classification of Hormones Figure 18.2

Major Pituitary Gland Hormones

Three Methods of Hypothalamic Control over the Endocrine System

The Anatomy and Orientation of the Pituitary Gland

The anterior lobe (adenohypophysis) Subdivided into the pars distalis, pars intermedia and pars tuberalis At the median eminence, neurons release regulatory factors through fenestrated capillaries Releasing hormones Inhibiting hormones

Feedback control of Endocrine Secretion

Feedback control of Endocrine Secretion

Negative Feedback Inhibition Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones

Hormones of the adenohypophysis Thyroid stimulating hormone (TSH) Triggers the release of thyroid hormones Thyrotropin releasing hormone promotes the release of TSH Adrenocorticotropic hormone (ACTH) Stimulates the release of glucocorticoids by the adrenal gland Corticotrophin releasing hormone causes the secretion of ACTH

Hormones of the adenohypophysis Follicle stimulating hormone (FSH) Stimulates follicle development and estrogen secretion in females and sperm production in males Leutinizing hormone (LH) Causes ovulation and progestin production in females and androgen production in males Gonadotropin releasing hormone (GNRH) promotes the secretion of FSH and LH

Hormones of the adenohypophysis Prolactin (PH) Stimulates the development of mammary glands and milk production Growth hormone (GH or somatotropin) Stimulates cell growth and replication through release of somatomedins or IGF Growth-hormone releasing hormone (GH-RH) Growth-hormone inhibiting hormone (GH-IH)

Melanocyte stimulating hormone (MSH) May be secreted by the pars intermedia during fetal development, early childhood, pregnancy or certain diseases Stimulates melanocytes to produce melanin

The posterior lobe of the pituitary gland (neurohypophysis) Contains axons of hypothalamic nerves neurons of the supraoptic nucleus manufacture antidiuretic hormone (ADH) Decreases the amount of water lost at the kidneys Elevates blood pressure

The posterior lobe of the pituitary gland (neurohypophysis) Neurons of the paraventricular nucleus manufacture oxytocin Stimulates contractile cells in mammary glands Stimulates smooth muscle cells in uterus

Growth Hormone Effects Protein Anabolic Increased plasma phosphorus Increase absorption of calcium in gut Diabetogenic Growth Periods Dwarfism Giantism Acromegly

Giantism Excessive Production during childhood Different systems respond differently

Acromegly Progression of untreated acromegly irregular bone growth continues

Acromegly Hands Feet Jaws Shows the characteristics Abnormal size.

The Thyroid Gland

The Thyroid Gland

Thyroid and Parathyroid Glands Shaped like a shield and lies just below the Adam’s apple in the front of the neck. Thyroxine helps set basal metabolic rate by stimulating the rate of cell respiration. In children, thyroid hormones also promote growth and stimulate maturation of the central nervous system. unique function in amphibians - metamorphosis from larvae into adults

Thyroid follicles and thyroid hormones Thyroid gland contains numerous follicles Release several hormones such as thyroxine (T4) and triiodothyronine (T3) Thyroid hormones end up attached to thyroid binding globulins (TBG) Some are attached to transthyretin or albumin

The Thyroid Follicles

Formation and secretion of thyroglobulin by the thyroid cells Thyroid cells are typical protein-secreting glandular cells The ER and GA synthesize and secrete into the follicles a large glycoprotein called thyroglobulin (TG) (Mr Wt 335,000) Each TG contains about 70 tyrosine a.a Thus TH formed within TG molecule

Oxidation of the Iodide Ion First step is the conversion of Iodide ions to an oxidized form of iodine either as Io or I- Oxidation of iodine is promoted by the enzyme peroxidase The enzyme is located either in apical membrane or attached to it

Iodination of Tyrosine and Formation of the Thyroid Hormones Binding of iodine with the TG is called Organification of the TG Enzyme Iodinase oxidises iodine within seconds Tyrosine is first iodized to monoiodotyrosine and then to diiodotyrosine Thus forming thyroxine that becomes the part of TG Or one molecule of monoiodotyrosine couples with one molecule of diiodotyrosine to form triiodotyronine

The Thyroid Follicles

Thyroid hormones Held in storage Bound to mitochondria, thereby increasing ATP production Bound to receptors activating genes that control energy utilization Exert a calorigenic effect

The Parathyroid Glands

Thyroid and Parathyroid Glands Parathyroid gland and calcium homeostasis four small glands attached to the thyroid produces parathyroid hormone (PTH) one of only two hormones in humans that are absolutely essential for survival stimulates osteoclasts in bone to dissolve calcium phosphate crystals and release Ca++ into the blood

Regulation of Blood Calcium Levels

Hypothyroidism Myxedema

Cretinism Infancy onset Persists throughout life Severe mental retardation

Infantile Cretinism Megaglossal tongue Druppy eyelids Lack of genital development Severe mental retardation

Hyperthroidism Graves Disease Wasting of Temporalis and shoulder muscle Myxedema in limbs

Graves Disease

Exothalamia Fat accumulation behind eyes High TSH Patient previously had a thyroidectomy

REFERENCES TEXT BOOK OF MEDICAL PHYSIOLOGY, ELEVENTH EDITION (2006), Arthur C. Guyton and John E. Hall. (Chapter -74,75 & 76). HUMAN PHYSIOLOGY by Wikibooks contributors. (http://en.wikibooks.org/wiki/Human_Physiology)