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

HYPOPHISISHormones of the adenohypophisisRegualation of the AdenoHy hormonesHormones of the neuroHyPituitary 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 Located inferior to the talamus Represents the ventral region of

the midbrain Center of homeostasis

GENERAL PRESENTATION 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 (GnRH). The neurons that secrete GnRH 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 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 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 Medial Area Anterior Medial preoptic nucleu

s

Supraoptic nucleusParaventricular nucleus

Anterior nucleusSuprachiasmatic nucleus

Tuberal Dorsomedial nucleus

Ventromedial nucleusArcuate nucleus

Posterior Mammillary nuclei

(part of mammillary bodies)Posterior nucleus

- Lateral AreaAnteriorLateral preoptic nucleusLateral nucleus Part of supraoptic nucleusTuberalLateral nucleusLateral tuberal nucleiPosteriorLateral nucleus

Hormones of the hypothalamus

Corticotropin-releasing hormone (CRH) Dopamine Gonadotropin-releasing hormone (GnRH) Growth hormone releasing hormone

(GHRH) Somatostatin Thyrotropin-releasing hormone (TRH) Hypocreatin Antidiuretic Hormone (ADH)

HT role in obesity 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 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)/height2 (in m) Waist/hip circumference = ratio of waist circumference to that of the

hips

HIPOPHYSIS (pituitary gland) 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

NEUROHYPOPHYSISConnected with the hypothalamus

via the hypophyseal tract

HORMONES OF THE ADENOHYPOPHISIS

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 – T3; thyroxine – T4)

Regulation by negative feedback ( high concentration of T3 and T4 in blood)

Gonadotropines (FSH, LH)

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 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 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

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

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

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)

Prolactin Stimulates milk secretion in

mammary glands previously prepared for milk production by other hormones – estradiol, progesterone, corticosteroids, insulin

Beta-lipoprotein 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

Secreted in small quantities by the intermediate lobe of pituitary gland

Role in skin pigmentation

Regulation of the adenohypophyseal hormones 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 adenoHY

Hormone Abreviation Function

Thyrotropin releasing hormone

TRH Stimulates release of TSH

Corticotropin releasing hormone

CRH Stimulates release of ACTH

Gonadotropin releasing hormone

GnRH 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 2 chemically similar peptide

hormones, ocytocin and antidiuretic hormone are called neurosecretions because are synthetised in hypotalamic neurons and stored in the neuroHY

When action potentials causes their release from axons they enter the blood and act as hormones.

Oxytocin 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) 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 disodersDisorder 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

Panhypopituitarism

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

ReminderGlands Hormones Target cells Major effects Negative

feedbackdisorders

Adenohypophisis

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

Testes

Maturation of ova; production of estrogenMaturation of sperm

Estrogen

Inhibin

Luteinizing hormone (LH)

Ovaries

Testes

Release of ova; production of progesteroneDevelopment of interstitial cells and production of testosterone

Progesterone

Testosterone

Adrenocorticotropic hormone (ACTH)

Adrenal cortex

Release of hormones from adrenal cortex

Cortisol

Thyroid stimulating hormone (TSH)- thyrotropin

Thyroid gland Synthesis and release of T3, T4

T3, T4

ReminderGlands Hormones Target cells Major effects Negative

feedback

Neurohypophisis Oxytocin Smooth muscle of uterus and mammary ducts

Cause uterine contraction and release of milk

Antidiuretic hormone (ADH)-vasopresin

Kidney tubulesSmooth muscle of blood vessels

Water reabsorbtionConstrict blood vessels and raise blood pressure

REFERENCES Avramescu ET, Rusu L., Ciupeanu – Calugaru D., 2005, Human

Anatomy, Universitaria Publishing House, Craiova, 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