FUNCTIONAL ANATOMY AND PHYSIOPATHOLOGY OF HYPOTHALAMUS AND ADENOHYPOPHISIS

FUNCTIONAL ANATOMY AND PHYSIOPATHOLOGY OF HYPOTHALAMUS AND ADENOHYPOPHISIS PHYSIOTHERAPY IN ENDOCRINE PATHOLOGY

Outline and objectives of the course Outline Objectives HYPOTHALAMUS -Describe the location, structure and function of the hypothalamus -Describe the hormons of the hypothalamus HYPOPHISIS Hormones of the adenohypophisis Regualation of the Adeno. Hy hormones Hormones of the neuro. Hy Pituitary disorders -Explain the functions of anterior pituitary hormones and how they are regulated -Explain the functions of posterior pituitary hormones and how they are regulated - Summarise the characteristics of pituitary disorders

HYPOTHALAMUS STRUCTURE

OVERVIEW n n n Located inferior to the talamus Represents the ventral region of the midbrain Center of homeostasis

GENERAL PRESENTATION n n The hypothalamus (from Greek ὑποθαλαμος = under the thalamus) is a region of the mammalian brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. The hypothalamus links the nervous system to the endocrine system via the pituitary gland, also known as the "master gland, " by synthesizing and secreting neurohormones, often called releasing hormones, as needed that control the secretion of hormones from the anterior pituitary gland — among them, gonadotropin-releasing hormone (Gn. RH). The neurons that secrete Gn. RH are linked to the limbic system, which is primarily involved in the control of emotions and sexual activity. The hypothalamus also controls body temperature, hunger, thirst, and circadian cycles.

GENERAL PRESENTATION n The hypothalamus co-ordinates many seasonal and circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and many important stereotyped behaviours. The hypothalamus must therefore respond to many different signals, some of which are generated externally and some internally. The hypothalamus is thus richly connected with many parts of the CNS, including the brainstem reticular formation and autonomic zones, the limbic forebrain (particularly the amygdala, septum, diagonal band of Broca, and the olfactory bulbs, and the cerebral cortex).

FUNCTION n n n n The hypothalamus is responsive to: Light: daylength and photoperiod for generating circadian and seasonal rhythms Olfactory stimuli, including pheromones Steroids, including gonadal steroids and corticosteroids Neurally transmitted information arising in particular from the heart, the stomach, and the reproductive tract Autonomic inputs Blood-borne stimuli, including leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines, plasma concentrations of glucose and osmolarity etc Stress Invading microorganisms by increasing body temperature, resetting the bodys thermostat upward.

The hypothalamus is a very complex region, and even small nuclei within the hypothalamus are involved in many different functions. The paraventricular nucleus contains oxytocin and vasopressin neurons which project to the posterior pituitary, but also contains neurons that regulate ACTH and TSH secretion (which project to the anterior pituitary), gastric reflexes, maternal behavior, blood pressure, feeding, immune responses, and temperature.

Hypothalamic nuclei -n n n n Medial Area Anterior Medial preoptic nucleus Supraoptic nucleus Paraventricular nucleus Anterior nucleus Suprachiasmatic nucleus Tuberal Dorsomedial nucleus Ventromedial nucleus Arcuate nucleus Posterior Mammillary nuclei (part of mammillary bodies) Posterior nucleus Lateral Area Anterior Lateral preoptic nucleus Lateral nucleus Part of supraoptic nucleus Tuberal Lateral nucleus Lateral tuberal nuclei Posterior Lateral nucleus

Hormones of the hypothalamus Corticotropin-releasing hormone (CRH) Dopamine Gonadotropin-releasing hormone (Gn. RH) Growth hormone releasing hormone (GHRH) Somatostatin Thyrotropin-releasing hormone (TRH) Hypocreatin Antidiuretic Hormone (ADH)

HT role in obesity n An important aspect of hypothalamic autonomic control with regard to the endocrine system is the control of food intake. The effects of obesity on endocrine function can be widespread and endocrine abnormalities can cause obesity. A number of hormones play central roles in the control of food intake

Measures of obesity n n n Three main experimental measures of fat mass in man have been used for many years. They require the determination of body density, water or potassium content and the assumption that the body composition can be divided into fat and fat-free or lean body mass with certain characteristics. These techniques are relatively costly, time-consuming and do not give information on the distribution of the fat. Techniques such as bioelectrical impedance rely on the fact that fat is not as good an electrical conductor as lean body mass. It is cheap but also does not allow an assessment of the distribution of the fat mass. Imaging techniques such as CT or MR allow the determination of fat from a number of tomographic 'slices' of the body. The distribution of the fat mass can be calculated. Simple anthropomorphic measurements such as height and weight allow the calculation of body mass index (BMI), whilst calipers can be used to measure subcutaneous fat. BMI = body weight (in kg)/height 2 (in m) Waist/hip circumference * = ratio of waist circumference to that of the hips

HIPOPHYSIS (pituitary gland) n n O, 5 -0, 8 G anterior pituitary (adenohypophysis) posterior pituitary (neurohypophysis) Regulated by hypothalamus – providing anatomical and physiological connections between nervous and endocrine system

ADENOHYPOPHYSIS Connected with the hypothalamus via the hypophyseal portal system NEUROHYPOPHYSIS Connected with the hypothalamus via the hypophyseal tract

HORMONES OF THE ADENOHYPOPHISIS n n n Somatotropin (growth hormone) Prolactin Gonadotropines: follicle-stimulating hormone (FSH); luteinizing hormone (LH) Thyroid stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH)

Thyrotropin Stimulates the thyroid gland to synthetize and secrete its hormones (triiodothyronine – T 3; thyroxine – T 4) Regulation by negative feedback ( high concentration of T 3 and T 4 in blood) n

Gonadotropines (FSH, LH) n n FSH stimulates the maturation of an ovum each month during a female reproductive years Stimulates maturation of sperm in males Stimulates production of estrogen hormones Regulation by negative feedback ( high concentration of estrogensin blood)

LH n n Stimulates ovulation and causes follicular cells to produce progesterone which stimulates nidation and mammary gland development In males stimulates development of interstitial cells (Leydig) of testis; stimulates production of testosterone

Somatotropin n n Acts directly on some cells to stimulate growth Acts indirectly on others to release proteins (insulin like growth factor I) Promotes calcium absorbtion from intestine Works with insulin and thyroid hormones to promote collagen synthesis

n n n Increase the rate at wich cells take up aminoacids and use them to synthetise proteins Stimulate free fatty acid release from fat cells and glycogen breakdown in the liver Stimulate growth to adult size

n n n Bone and muscle loss associated with reduced strength in aging may be due to declining GH after age 50. At age 30 – body mass: 10% bone, 30% muscle, 20% fatty tissue At age 75 - body mass: 8% bone, 15% muscle, 40% fatty tissue

Corticotropin(ACTH) Acts on the cortex of the adrenal gland to regulate synthesis and secretion of several of its hormones, especially glucocorticoids n Glucocorticoids stimulate the release of fatty acids and glucose into the blood and help the body to resist stress and inflamation Regulation by negative feedback ( high concentration of cortisol in blood) n

Prolactin n Stimulates milk secretion in mammary glands previously prepared for milk production by other hormones – estradiol, progesterone, corticosteroids, insulin

Beta-lipoprotein n n Has been isolated from the anterior pituitary gland Endorphins and enkefalins can be made from it in the anterior pituitary or in the brain directly

Melanocyte stimulating hormone n n Secreted in small quantities by the intermediate lobe of pituitary gland Role in skin pigmentation

Regulation of the adenohypophyseal hormones n n By neurohormones secreted by hypothalamus (releasind and inhibiting) Tropic hormones from the anterior pituitary regulate other glands such as the thyroid, adrenal cortex, gonads Hormones from these glands act by negative feedback to inhibit the release of both tropic and hypothalamic hormones Neural signals elicited by sexual arousal, stress, anxiety, trauma, variations in the light-dark cycle and the sucking of a breast-fed infant also regualte hypothalamus hormones

Hypothalamic hormones that regulate secretion of adeno. HY Hormone Abreviation Function Thyrotropin releasing hormone TRH Stimulates release of TSH Corticotropin releasing hormone CRH Stimulates release of ACTH Gonadotropin releasing hormone Gn. RH Stimulates release of FSH and LH Growth hormone releasing hormone GHRHH Stimulates release of GH Growth hormone inhibiting hormone (somatostatin) GHIH Inhibits release of GH Prolactin releasing hormone PRH Stimulates release of prolactin Prolactin inhibiting hormone PIH Inhibits release of prolactin

Hormones of the neurohypophysis n n 2 chemically similar peptide hormones, ocytocin and antidiuretic hormone are called neurosecretions because are synthetised in hypotalamic neurons and stored in the neuro. HY When action potentials causes their release from axons they enter the blood and act as hormones.

Oxytocin n n Stimulates contraction of smooth muscle in the uterus and the contractile cells around mammary gland ducts Is relased during sexual intercourse, labor, lactation

Antidiuretic hormone (ADH) n n n Also called vasopresine Prevents excess water loss in urine In high concentrations constricts blood vessels Decreases osmotic pressure and the urine volume Increases the blood volume

Pituitary disoders Disorder Possible cause Hormone Excess or defficiency Effects Pituitary dwarfism Destruction or congenital defficiency of GH production cells GH defficiency Small, well proportioned body, sexual imaturity Gigantism Pituitary tumor before adult size is reached GH excess Large, well proportioned body Acromegaly Pituitary tumor after adult size is reached GH excess Disproportionate increase in thickness of bones of face, hands and feet Panhypopituit arism Tumor or thrombus all defficiency Depressed thyroid, adrenocortical and gonad function Diabetes insipidus Damage to the hypothalamus ADH defficiency Excessive excretion of dilute urine High ADH blood level Excessive stimulation of ADH-secreting neurons or pituitary tumor ADH excess Excessively dilute blood and low sodiun concentration in plasma

Reminder Glands Hormones Target cells Major effects Negative feedback disorders Adeno hypophisis Growth hormone (somatotropin) Most cells growth, maintanence of adult size, protein synthesis, release of fats and glucose into blood Blood nutrient level Dwarfism, gigantism, acromegaly Prolactin Mammary glands Secretion of milk Follicle stimulating hormone(FSH) Ovaries Maturation of ova; production of estrogen Maturation of sperm Estrogen Release of ova; production of progesterone Development of interstitial cells and production of testosterone Progesterone Testes Luteinizing hormone (LH) Ovaries Testes Inhibin Testosterone Adrenocorticotropic hormone (ACTH) Adrenal cortex Release of hormones from adrenal cortex Cortisol Thyroid stimulating hormone (TSH)thyrotropin Thyroid gland Synthesis and release of T 3, T 4

Reminder Glands Hormones Target cells Major effects Neurohypophisis Oxytocin Smooth muscle of uterus and mammary ducts Cause uterine contraction and release of milk Antidiuretic hormone (ADH)vasopresin Kidney tubules Smooth muscle of blood vessels Water reabsorbtion Constrict blood vessels and raise blood pressure Negative feedback

REFERENCES n Avramescu ET, Rusu L. , Ciupeanu – Calugaru D. , 2005, Human Anatomy, Universitaria Publishing House, Craiova n n n , Bello M. , Testing the effects of growth hormone releasing hormone, Research Resources 9, no 10: 1, 1985 Creager J. , 1992, Wm. C. Brown Publisher Lechan, R. , Neuroendocrinology of pituitary hormone regulation, Endocrinology and Metabolism Clinics 16, no 3: 475, 1987