Physiology of the Pituitary Gland PDF

# Physiology of the pituitary Gland Mohamed Barhoma [email protected] ## Department of Physiology Menofia National University Egypt October 8, 2024 ## Outline 1. ILOs 2. Hypothalamic hormones 3. Introduction to pituitary 4. Anterior Pituitary * Feed back Mechanism * Melanocyte...

# Physiology of the pituitary Gland Mohamed Barhoma [email protected] ## Department of Physiology Menofia National University Egypt October 8, 2024 ## Outline 1. ILOs 2. Hypothalamic hormones 3. Introduction to pituitary 4. Anterior Pituitary * Feed back Mechanism * Melanocyte stimulating hormone 5. Growth Hormone * Somatomedins 6. Disturbance in anterior pituitary 7. Posterior pituitary gland (neurohypophysis) 8. diabetes insipidus ## Intended learning objectives (ILOs) By the end of this lecture, the student should be able to: * know the Hypothalamic-hypophyseal connection * know the different parts of the pituitary gland * know the different hormones produced by each partial and its functions * know the relation between the hypothalamus and the pituitary gland * understanding the control and regulation of the pituitary hormones * identify the possible disturbances in these hormones and how to manage it * differentiate between different cases of short status * differentiate between diabetes insipidus and diabetes meletus ## Hypothalamic Hormones * Growth hormone releasing hormone * Growth hormone inhibiting hormone * Corticotropin releasing hormone * Thyrotropin releasing hormone * Gonadotropin releasing hormone * Prolactin releasing hormone * Prolactin inhibiting hormone ## Introduction to pituitary ### Pituitary gland (The Hypophysis) This is a small gland, about 0.5-1 gm in weight, situated at the base of the brain in a small cavity in the skull called sella turcica and is attached to the floor of the 3rd ventricle of the brain by a stalk, in consists of 3 lobes which are anterior lobe, middle lobe and posterior lobe. ### Hypothalamic connection of the pituitary gland There are 2 types of connections between the hypothalamus and the pituitary gland. This connection is a form of connection between the nervous system and the gland. These connections are: 1. Vascular connection between the hypothalamus and the pituitary gland called hypothalamo-hpophyseal portal circulation 2. Nervous connection between the hypothalamus and the posterior pituitary gland in the form of hypothalmo-hypophyseal tract. ## Anterior Pituitary ### The Anterior pituitary gland (Adeno-hypophysis) This gland is called the master gland, as it regulates most of other body glands and it secretes several hormones which are: 1. Adrenocorticotropic hormone (ACTH) 2. Prolactin (lactogenic hormone) 3. Growth hormone (somatotropin hormone) 4. Melanocyte stimulating hormone (gamma form) 5. Thyroid stimulating hormone (TSH) 6. Luteinizing hormone (LH) 7. Follicular stimulating hormone (FSH) ### Notes * **Intermediate lobe** - This lobe is rudimentary in human, and it secretes alpha, beta, and gamma melanocyte stimulating hormone * **Posterior lobe** - This lobe considers the storage and site of release of both antidiuretic hormone (ADH) and oxytocin hormone. ### Control of the anterior pituitary secretion 1. The secretion of the anterior pituitary is controlled by both the hypothalamus and the feedback mechanisms 2. Hypothalamus regulates the anterior pituitary gland by releasing certain hormones called hypophyseotropic hormone which secretes from the median eminence 3. These hormones are polypeptide in nature and reach the anterior pituitary via hypothalamic-hpophyseal portal circulation and they ↑ the intracellular cAMP in the cell of the anterior pituitary gland. ### Enrichment knowledge * Because hypothalamus is connected to several areas in the brain, so it regulates many functions of the body via the hypothalamic hormones through releasing hypothalamic hormones. So, psychological stress and disturbance are usually associated with endocrine disturbances. * Usually, hypothalamus regulates the activities of pituitary through regulating (releasing or inhibiting) hormones. ### Feed back Mechanism This is the relation between the hormonal blood level and the secretary rate of pituitary tropic hormone and hypothalamic hormones, it's of two types: 1. **Positive feedback:** If the blood level of a certain hormone increases, it stimulates the secretion of the pituitary tropic or hypothalamic releasing hormone. 2. **Negative feedback:** In this relation, if the blood level of a certain hormone increases, it rapidly decreases to its normal level and vice versa if it decreases, this mechanism occurs in two ways. ### Types of Feedback Mechanism * **Long loop negative feedback:** This is the direct effect of the circulating hormone on the rate of secretion of either the pituitary or on the hypothalamic hormones or both together. For example, if the thyroid hormone level increases, it will reduce both TSH and TRH. * **Short loop negative feedback:** In this mechanism, the high level of circulating hormone may also control the pituitary tropic hormone itself, which suppresses the hypothalamic secretion through short circulation¹. * **Ultra-short or auto regulation:** The increased level of the hypothalamic hormone suppresses the extra release of the hypothalamic hormones. _¹Hypothalamic-hypophysealportal circulation_ ### Melanocyte Stimulating hormone This hormone is of great importance in regulating skin coloration, especially fish, reptiles and amphibian through the production of melanin. Melanin is of two types: * **Eumelanin** - which is responsible for black coloration * **Pheomelanin** - which is responsible for red and yellow coloration of the skin In animals, this action occurs through melanophore, while in humans there is no melanophore, but the action occurs through melanocytes, which secrete melanin and cause dark skin coloration. They act through increased cAMP in the cell, as they are protein in nature, and their receptors are present in the cell membrane of their target organs. Catecholamine and melatonin are whitening hormones, while the melanin is the darkening hormone. ## Growth Hormone ### Growth hormone regulation This is a protein hormone resembling in structure to prolactin hormone. ### Growth Hormone **Action:** Consider the major growth promoting factor and exerts many anabolic effects and has lactogenic activity due to its resemblance to the prolactin hormone. * Growth involves an ↑ in the body mass through increasing both cell division and protein synthesis. * This results in an ↑ in tissue size and length, and weight. Growth hormone stimulates several tissues, including bone, muscle, and viscera, but it has no effect on metamorphosis (which is the function of thyroxine hormone). So, young animal growth is affected by the deficiency of the growth hormone. Growth hormone effects on bone growth, especially on cartilaginous discs. ### Effect of Growth hormone on Metabolism * **Electrolyte Metabolism:** GH↑ the intestinal absorption of calcium, and produces a positive phosphorus balance and also↓ the rate of urinary excretion of Na⁺ and K⁺. This sparing effect for electrolytes is important for the growing tissue. * **Protein Metabolism:** GH has anabolic hormone² and causes a fall in the blood level of urea and amino acids. * **Fat Metabolism:** It ↑ the blood level of both free fatty acid and ketone bodies. This occurs by mobilization of fatty acids from adipose tissue to blood and inhibits the insulin lipogenic effect. _²Produce positive nitrogen balance._ ### Follow Effect of GH on Metabolism The growth hormone has a diabetogenic effect³. * ↑ hepatic glucose output through activating glucose-6 phosphatase enzyme. * Exerting an anti-insulin effect. It ↓ the glucose uptake by cells, especially skeletal muscle. This is through reducing the ability of tissue to bind insulin and probably to reduce the insulin receptors. These actions result in ↓ the glucose entrance to the cell. * Inside the cell growth hormone inactivates hexokinase enzyme so ↓ glucose phosphorylation. _³That leads to an ↑ in the glucose level_ ### Enrichment knowledges **Important Notes** Growth hormone ↑ the sensitivity of pancreas to insulin stimuli like glucose and arginine, and thus, after the hormone ↑ the glucose, it stimulates insulin release and so this considers another way for increasing growth. ### Action of Growth hormone * Liver and other organs * Somatomedins * Skeletal tissue * chondrogenesis * Skeletal growth * Growth promoting action * Extra skeletall * Thyroxine * Tissue differentiation * Metabolic Action * Growth hormone * Cortisol * Protein * Fat * Carbohydrates * Positive nitrogen balance * ↑ Lipoprotien * ↑ blood glucose ### Somatomedins They are polypeptides growth factor that secreted by liver and other tissues in response to growth hormone stimulation. There are several types of somatomedins: * **IGF-I or insulin-like growth factor I or somatomedin C** - which is more growth hormone dependent * **IGF-II or insulin-like growth factor II** - which is growth hormone independent, and it may only play a role in fetal growth. **Note:** Growth hormone does not produce a direct growth effect, but it is believed that it just has permissive action for IGF-I, e.g. on bone it just acts on the stem cell to make them sensitive to IGF-I, which makes the growth itself. ### Control of growth Hormone secretion * Hypothalamus * GRIH * GRRH * Anterior pituitary * Gland * Growth Hormone * Target organs * Somatomedins ### Control of Growth hormone secretion Growth hormone is controlled by two hypophyseotropic hormones (GRH and GIH), and the rate of its secretion undergoes marked fluctuations in response to a variety of stimuli. **Stimuli that affect Growth Hormone:** 1. Deficiency of the energy-producing substance like glucose or increased demands for them, like in exercise. 2. Increase of certain amino acids, like arginine. 3. Stressful stimuli. 4. Going to sleep. 5. Glucagon. ### Follow Control of Growth hormone secretion **Stimuli That ↓ GH:** 1. Increase blood glucose level 2. Increase cortisol level 3. Increased blood level of free fatty acids **Other hormones that affect growth:** * **Thyroid hormone:** It has no direct effect on growth, but its effect is mainly permissive to growth hormone and potentiating of somatomedins. * **Glucocorticoids:** At normal levels, these hormones have permissive action for growth hormone, however, glucocorticoid has direct catabolic action. * **Insulin:** Diabetic animal fail to grow. This is due to the lack of the anabolic effect of insulin. * **Sex hormone:** These hormones cause growth at puberty because they have anabolic effects. This is mainly due to androgens, but later on, they may stop growth due to the epiphyseal fusion. ### Causes of short status (stunted growth) 1. **Deficient GH:** This may occur due to pituitary disease or defect at the hypothalamic level. If the deficiency is accompanied with deficient GTH, this results in infantilism. 2. **Cretinism**. 3. **Laron dwarfism:** This occurs due to severe liver disease, however, there is a normal or even elevated level of Growth hormone. But, the short status may occur due to deficiency of the circulating somatomedins. 4. **Precocious puberty**. **Note:** The commonest causes of short status are cretinism, dwarfism and infantilism. Cretinism is the worst condition. ## Disturbance in anterior pituitary ### Disturbance in Master gland 1. **Excessive secretion of GH:** This results from tumor which secretes large amounts of GH. It produces two diseases, Gigantism in children and acromegaly in adults. * Gigantism * Acromegaly 2. **Deficient secretion of GH:** * Pituitary dwarfism * Pituitary infantilism * Pituitary hypofunction * Partial pituitary insufficiency * Panhypopituirism (Simmond's disease). ### Gigantism **Etiology of Gigantism:** This disease is due to excessive secretion of growth hormone in pre-adult life (in children), before epiphyseal closure, and it is characterized by: 1. **Abnormal height:** Excessive growth of long bones results in abnormal height, with a huge status and the animal becomes ‘giant’. 2. In humans, there are large hands and feet. 3. **Coarse facial features:** thick lips, macroglossia, and thickness 4. **Bilateral gynecomastia** (Enlargement of breasts in males). 5. **Loss of libido/impotence**. 6. **Hyperglycaemia:** Caused by GH, it leads to excess insulin secretion. Overactivity of beta cells in the pancreas ultimately leads to degeneration of these cells and deficiency of insulin, resulting in diabetes mellitus. ### Follow Findings of Gigantism **Features due to tumor mass include:** 1. Headache, 2. Visual field defects, 3. Cranial nerve palsies 4. Enlargement of pituitary fossa, which may be detected on radiography of the skull. ### Follow Acromegaly * Overgrowth of viscera, splenomegaly, and other soft tissues, like lips, nose, forehead and scalp, are thickened. The skin becomes thickened and wrinkled (bulldog scalp). * **Hirsutism:** Increased body hair. * 25% of the patients show diabetes due to the diabetogenic effect of growth hormone * **Gynecomastia:** Which means enlargement of the breasts in males and lactation in 4% of females. * In advanced cases, the gonads may be affected due to pressure atrophy of the tumor on the gonadotropic cells of the pituitary. * Local effects of the tumor may lead to changes in the visual fields, headache, blurring of vision, and vomiting. ### follow Acromegaly * **Figure: Acomegaly:** * (a) prognathism * (b) prognathism2 * (c) kyphosis * (d) Acromegalic hand * **Figure: Hirsatisum** * **Figure: hisrsatism2** ## Deficient secretion of GH Deficiency in young individuals causes dwarfism or infantilism, while in adults it causes some protein loss. ### Pituitary dwarfism This disease is due to the decrease in secretion of the growth hormone before puberty and it's characterized by the following: 1. **Arrest in growth** due to rapid union of epiphysis and diaphysis. So, the person is with short stature. Their height does not exceed 120cm in adult life. 2. The stunting in skeletal growth is symmetrical so the body proportion is like a child. But, they have a relatively large head compared to body size. 3. The growth of soft tissue is retarded with a tendency to be obese. 4. **Lowered metabolic rate**. 5. **Mental development is normal**, usually intelligent, with tendencies to be emotionally unstable. There is normal sexual maturity if GH is only deficient. ### dwarfism * **Figure: dwarfism:** * (a) dwarf * (b) dwarf1 ### Pituitary infantilism In this case, there is a deficiency in GH, besides GTH. So, there is dwarfism with failure to develop in sexual organs. ### Pituitary hypofunction This is insufficiency secretion of the pituitary gland, and this insufficiency can be partial or complete. ### Pituitary insufficiency **Partial pituitary insufficiency:** The pituitary gland has a large reserve of hormone, so much of the gland can be destroyed without producing endocrine abnormalities. The first hormone affected is GH, then GTH. Then, thyroid and finally ACTH when 100% of the gland is impaired. **Panhypopituirism (Simmond's disease):** This is a generalized failure of the anterior pituitary gland, and, since it is the master gland, this disease is characterized by: 1. **Arrest in growth**. 2. **Hypoglycemia** due to decrease in insulin antagonist effects of growth hormone. 3. **Depressed activity of thyroid gland** leading to low metabolic activity. 4. **Depressed activity of adrenal cortex** makes the patient unable to withstand stress. 5. **Severe pallor** due to anemia and deficiency of ACTH and MSH. 6. **Depressed GTH** leads to the depressed sex cycle in females and impotence in males. 7. **Deterioration of the mental function**. 8. **Anorexia**, and loss in body weight. **Progeria** (premature senility) ## Posterior pituitary gland (neurohypophysis) ### Posterior pituitary gland (neurohypophysis) Two hormones are released (not secreted) from posterior pituitary glands - these hormones are (ADH) or vasopressin and oxytocin hormone. These hormones are polypeptide hormones which are secreted for hypothalamic nucleus uses, ADH is secreted from the supraoptic nucleus, while oxytocin is secreted from the paraventricular nucleus. These hormones, after their synthesis, move along the neural axon to the posterior lobe of the pituitary and stored till their release. _kidey nephron_ **On Kidneys:** It increases water reabsorption from the renal tubules, leading to water retention in the body. So, the urine becomes concentrated, and its volume is decreased (antidiuretic effect). The main site of action of this hormone in the kidney is on the collecting tubules in which the ADH acts on receptors called V2 receptors. This combination leads to an increase in the cyclic –AMP, which in turn leads to opening of many protein water channels in the collecting tubules. This, in turn, leads to passive reabsorption of water due to high osmotic pressure in the renal medulla. ### Site of ADH action in kidney * Cortex * Medulla * Proximal tubule * Distal tubule * Glomerelus * Ureter * Loop of Henle * Collecting duct * Medulla * Cortex * In some nephrons, the loop of Henle is long and plunges into the medulla. * Final urine to ureter * **Figure: kidney cortex and Medulla** - go back ### Function of ADH **On the blood vessels:** This hormone has a direct powerful vasoconstriction in large doses, which ↑ the peripheral resistance. This action occurs through its effects on the V1 receptor, which are present in the arterial wall. **Factors that Control the release of ADH:** **Plasma Osmolality:** The release of ADH is controlled by a feedback mechanism that maintains the plasma molarity with the normal range. Minimal change in plasma osmotic (1%) pressure results in significant change in ADH. This action occurs through osmoreceptors, which are very sensitive to changes in plasma osmolality. These receptors are located in the hypothalamus. When the plasma osmotic pressure increases (dehydration) it leads to a discharging signal to the posterior pituitary through the hypothalamo-hypophyseal tract and, it results in the release of ADH. The reverse occurs when plasma osmotic pressure decreases, as in the case of overhydration. ### Control of ADH **Extracellular fluid volume** The change in the ECF volume also results in the release of ADH; this is mediated through affecting certain receptors in the low and high-pressure portions of the vascular system. The low-pressure receptors are located in the atria, great veins, and pulmonary vessels, while the high-pressure receptors (baroreceptors) are present in the carotid sinus and aortic arch. **Control of ADH** Reduction in the ECF also leads to the production of angiotensin II, which also releases ADH. **High pressure Receptors** The high-pressure receptors act in a similar way to low-pressure receptors, however, they result in the release of ADH in the ECF in large quantities, enough to increase blood pressure. **N.B:** Hemorrhage is the most potent stimulus which results in the release of ADH. ## Diabetes insipidus ### Diabetes insipidus This is a disease caused by ADH deficiency due to lesions in the hypothalamic nuclei and hypothalamo-hypophyseal tract. Sometimes this disease occurs due to the inability of the kidney to respond to ADH. It is characterized by the following symptoms: * **Polyuria**, * **Polydipsia**, * **Loss of water-soluble vitamins in the urine** ### Difference between Diabetes mellitus and Diabetes insipidus | Polyuria polydipsia and thirst | Diabetes insipidus | Diabetes mellitus | | ---------------------------- | --------------------- | ------------------ | | | sever | Less severe | | Glycosuria | Absent | present | | Urine specific gravity | Very low (1002-1006) | High (1030) | | Urine color | Colorless | Lemon yellow | | Urine PH | Neutral | Acidic due to presence of keto-acidic acids | ## Oxytocin ### Oxytocin This is a polypeptide that is secreted mainly by the paraventricular nucleus of the hypothalamus and stored in the posterior pituitary till the time of their release. This hormone performs its actions through increasing the cellular calcium. ### Function and release of oxytocin 1. **Milk Ejection:** This is the most important function of the oxytocin hormone, through its effect on the myoepithelium, which is present in the milk ducts and wall of the alveoli and allows for the ejection of milk through the teat or nipples. ### Mechanism of Milk Ejection This occurs as a neurohumeral (neuroendocrine) reflex, and it happens as follows: * Suckling stimulates touch receptors around the teat or nipples. * These impulses are transmitted to the hypothalamus, which stimulates the release of oxytocin from the posterior pituitary as well as prolactin from the anterior pituitary. * Hypothalamus can also be stimulated by many other factors, like emotional stimuli and conditioned reflex. ### oxytocin 2. **Control of uterine smooth muscle:** Oxytocin generally causes contraction of smooth muscle in the pregnant, and non-pregnant uterus. However, the sensitivity of the uterine muscle to oxytocin increases with estrogen, and decreases with progesterone. During pregnancy, progesterone levels are high. This, in turn, makes the uterus quiet. This is important for maintaining pregnancy. At the end of pregnancy, the progesterone level is lowered due to lysis of the Corpus Luteum of pregnancy, and estrogen secretion increases. These two actions result in an increase in the sensitivity of the uterus to oxytocin, and uterine contraction starts. So, oxytocin plays an important role in labor induction and parturition, as well as the expulsion of the placenta. 3. **Sperm Transport in the female genital tract:** Transport of sperms in the female genital tract depends not only on sperm motility but also on the uterine, and fallopian tube contractility and motility. Oxytocin is released during sexual intercourse, which leads to sexual orgasm, as well as contraction that helps in the transport of sperms to the site of fertilization. 4. **In Males:** The function of oxytocin may cause a discharge of sperms from the seminiferous tubules and epididymis to the vas deferens. ## End Thank you.