Endocrine system Dicky Moch Rizal Dept Of Physiology

Endocrine system Dicky Moch Rizal Dept. Of Physiology, Fac. Medicine, GMU

Endocrine system maintains homeostasis The concept that hormones acting on distant target cells to maintain the stability of the internal milieu was a major advance in physiological understanding. The secretion of the hormone was evoked by a change in the milieu and the resulting action on the target cell restored the milieu to normal. The desired return to the status quo results in the maintenance of homeostasis

Endocrine vs. Nervous System • Major communication systems in the body • Integrate stimuli and responses to changes in external and internal environment • Both are crucial to coordinated functions of highly differentiated cells, tissues and organs • Unlike the nervous system, the endocrine system is anatomically discontinuous.

Nervous system • The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.

Hormones travel via the bloodstream to target cells • The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

A cell is a target because is has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone.

Principal functions of the endocrine system • Maintenance of the internal environment in the body (maintaining the optimum biochemical environment). • Integration and regulation of growth and development. • Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.

Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.

Response vs. distance traveled Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it.

Hormone receptors • Hormone receptor characteristic ▫ Distinguish their hormones from other molecules ▫ Bind to their hormones even the concentration hormone exceeding low ▫ Undergo a conformational change when bound to the hormone ▫ Catalyze biochemical events or transmit change in molecular transformation to adjacent moleculesthat produce a biochemical change

Human Physiology Endocrine System • Control pathways • May be ▫ Local pathways �Paracrine and autocrine responses �In or in the vicinity of the cells or tissues

▫ Long-Distance pathways �Response loops �Stimulus �Sensor/receptor �Afferent pathway �Integrating center �Efferent pathway �Effector �Responses

Human Physiology Endocrine System • Negative feedback loops ▫ Stabilizing a function and maintain it withing a normal range ▫ Response is in opposition to stimuli ▫ Homeostatic control

• Positive feedback loops ▫ Response reinforces the stimulus ▫ Response destabilizes the variable ▫ Requires an event outside the loop to stop them

Human Physiology Endocrine System Disturbance Negative feedback _ Controlled system Sensor Error signal Output Set-point adjuster Inverting amplifier

Human Physiology Endocrine System • Control systems vary in their speed & specificity ▫ Specificity �Nervous control very specific �Hormonal control more general ▫ Nature of signal �Nervous system uses both electrical and chemical �Endocrine system uses only chemicals

▫ Speed �Nervous system much faster, up to 120 m/sec �Endocrine system much slower ▫ Duration of action �Nervous system shorter, very brief �Endocrine system lasts longer

Human Physiology Endocrine System ▫It brings about changes via chemical messengers, hormones, released into the blood stream and carried to target organs. ▫Endocrinology - the study of hormones and the endocrine organs. ▫Endocrine system - all of the glands that secrete hormones �Endocrine and exocrine glands ▫Exocrine glands - have ducts through which their nonhormonal products travel to the membrane surface and to the exterior (epithelial surface)

Human Physiology Endocrine System ▫Endocrine glands - release their substances into the surrounding fluid (ductless glands). They include the pituitary, thyroid, parathyroid, adrenal, pineal, and the thymus glands. Also included are the pancreas and gonads. The hypothalamus is called a neuroendocrine organ. ▫Know Fig 7. 2

Inputs to endocrine cells

Neural control • Neural input to hypothalamus stimulates synthesis and secretion of releasing factors which stimulate pituitary hormone production and release

Chronotropic control • Endogenous neuronal rhythmicity • Diurnal rhythms, circadian rhythms (growth hormone and cortisol), Sleep-wake cycle; seasonal rhythm

Episodic secretion of hormones • Response-stimulus coupling enables the endocrine system to remain responsive to physiological demands • Secretory episodes occur with different periodicity • Pulses can be as frequent as every 5 -10 minutes

Episodic secretion of hormones • The most prominent episodes of release occur with a frequency of about one hour—referred to as circhoral • An episode of release longer than an hour, but less than 24 hours, the rhythm is referred to as ultradian • If the periodicity is approximately 24 hours, the rhythm is referred to as circadian ▫ usually referred to as diurnal because the increase in secretory activity happens at a defined period of the day.

Circadian (chronotropic) control

Human Physiology Endocrine System

Human Physiology Endocrine System, Hormones • Hormones - chemical messengers carried by the blood from endocrine glands to the cell upon which they act. ▫ Are chemical messengers ▫ Secreted into the blood by endocrine cells or neurons ▫ Affect distal targets

• Affect target cells by controlling ▫ ▫ Rate of enzymatic reactions Transport of molecules across cell membrane Gene expression and protein synthesis Stimulation of mitosis

Human Physiology Endocrine System, Hormones • Classification ▫ Peptide hormones - 3 or more amino acids ▫ Steroid hormones - derived from cholesterol ▫ Amine hormones - single amino acids • Know Table 7 -1

Human Physiology Endocrine System, Hormones • Classification, Peptide hormone - eg: Insulin ▫ Synthesis - RER, preprohormone ▫ Packaged in vescicles ▫ In Golgi apparatus, pre to pro hormone then to hormone and fragments ▫ Released into ECF when cell is signaled to do so ▫ Transported in blood, half-life - minutes

▫ Mechanism of action - bind to cell surface receptors. Many use c. AMP and some use tyrosine kinase ▫ Action - open or close membrane channels or modulate metabolic enzymatic activity or transport proteins

Human Physiology Endocrine System, Classification • Peptide hormone synthesis, packaging, and release Figure 7 -3

Human Physiology Endocrine System, Hormones • Classification, Steroid hormones, eg: estradiol ▫ ▫ Synthesis - SER, lipophilic, sythesized as needed Found bound (inactive) to protein carriers in blood Half-life - hours Mechanism - diffuses across cell membrane to cytoplasmic and nuclear receptors. Interact with DNA ▫ Slow response by cells - hours ▫ Fig 7. 7

Human Physiology Endocrine System, Hormones • Action of Steroid Hormones

Human Physiology Endocrine System, Hormones • Classification, Amine hormones ▫ Nitrogen-containing ▫ Most derived from tryptophan or tyrosine ▫ They behave like peptide hormones (catecholamines) or like steroid hormones (thyroid hormones) ▫ Thyroid hormones: produced by thyroid gland found in the lower part of the neck. It secretes 3 hormones: �Thyroxine - T 4 �Triiodothyromine - T 3 �Calcitonin ▫ The first two are collectively known as thyroid hormones (TH) and contain iodine ▫ Virtually every tissue in the body is affected by TH

Human Physiology Endocrine System, Hormones • Amine hormone, Adrenal medullary hormones ▫ The adrenal gland consists of a medullary and cortical section. The cortex secretes steroid hormones. ▫ The adrenal medulla secretes two hormones �Epinephrine (E) and �Norepinephrine (NE) ▫ These are also called catecholamines

Human Physiology Endocrine System, Hormones • Second messenger mechanisms of amino acidbased hormones

Human Physiology Endocrine System, Hormones • Steroid hormones ▫ Produced by the adrenal cortex, the gonads, and the placenta ▫ Precursor is cholesterol ▫ Synthesis of steroid hormones

Human Physiology Cholesterol Endocrine System Pregnenolone Progesterone 17 -Hydroxyprogesterone Dihydroepiandr♂sterone (Androgens) Androstenedione Testes Corticosterone (Glucorticoids) Aldosterone (Mineralocorticoid) Cortisol Testosterone Ovaries Estradiol

Human Physiology Endocrine System, Hormones • Direct gene activation mechanism of steroid hormones

Human Physiology Endocrine System, Hormones • Hormonal Specificity ▫ All major hormones circulate to virtually all tissues (target cells), but for these cells to respond to a hormone, they must have a specific protein receptor on their plasma membrane or in their interior.

• Hormone-target interaction depends on: ▫ Blood levels of the hormone ▫ The relative number of receptors for that hormone ▫ The affinity of the bond between the hormone and the receptor • Up-regulation and down-regulation

Human Physiology Endocrine System, Hormones • Onset, Duration, and Half-life ▫ Onset varies greatly, from almost immediately to hours or days ▫ Duration can range from several minutes to several hours ▫ Half-life is the length of time the hormone concentration takes to drop by half �From a fraction of a minute to several hours ▫ Concentration determined by its rate of release and the speed of deactivation and removal

Human Physiology Endocrine System, Control of Hormone Release • Endocrine glands are stimulated by humoral, neural and hormonal means. ▫ Humoral stimuli - changing levels of blood ions and nutrients. Example: -↓calcium →↑parathyroid hormone ▫ Neural stimuli - nerve fiber stimulates hormonal release. Example: -↑nervous input to adrenal medulla → release of catecholamines

• Hormonal stimuli (tropic hormones) - endocrine glands release their hormones in response to hormones produced by other endocrine organs. Example: -hypothalamic hormones → anterior pituitary to release hormones → other endocrine glands to produce even more hormones

Human Physiology Endocrine System, Neurohormones • Hypothalamic-pituitary system ▫ Pituitary gland - lies just below hypothalamus, in pocket of bone at base of brain. Consists of two adjacent lobes - the anterior pituitary and the posterior piruitary ▫ Posterior pituitary hormones �Oxytocin and vasopressin are released �Made in hypothalamus, move down the neural axons and accumulate in the axon terminals in the posterior pituitary �Vasopressin - blood pressure and kidney function �Oxytocin - breasts and uterine contractions

Human Physiology Endocrine System, Neurohormones • Hypothalamus and Anterior Pituitary ▫ The hypothalamus also secretes hormones that control the secretion of ALL the anterior pituitary hormones. The basic pattern is as follows: �Secretion of a hypothalamic hormone, which controls secretion of �An anterior pitiutary hormone, which controls the secretion of �A hormone from some other endocrine organ/gland ▫ Anterior Pituitary Hormones �At least eight secreted, six with well-established functions

Human Physiology Endocrine System, Neurohormones

Human Physiology Stimulus Endocrine System, Neurohormones Hypothalamus ↑Hormone 1 Secretion ↑Plasma Hormone 1 Anterior Pituitary ↑Hormone 2 Secretion ↑Plasma Hormone 2 Third Endocrine Gland ↑Hormone 3 Secretion ↑Plasma Hormone 3 Target Cells

Human Physiology Endocrine System • Hypothalamic Releasing Hormones ▫ ▫ Corticotropin Releasing Hormone (CRH) Thyrotropin Releasing Hormone (TRH) Growth Hormone Releasing Hormone (GHRH) Somatostatin (SS) also called Growth hormone releasing Inhibitin Hormone (GIH) ▫ Gonadotropin Releasing Hormone (Gn. RH) ▫ Prolactin Releasing Hormone (PRH) ▫ Prolactin releasing Inhibiting Hormone (PIH)

Human Physiology Endocrine System • Anterior Pituitary Hormones ▫ Gonadotropic Hormones �Follicle-Stimulating Hormone (FSH) �Luteinizing Hormone (LH) ▫ ▫ Growth Hormone (GH) Thyroid-stimulating Hormone (TSH) Prolactin Adreno. Cortico. Tropic Hormone (ACTH) ▫ β-Lipotropic Hormone ▫ β-Endorphin

Human Physiology Hypothalamus Gn. RH FSH and LH Gonads Germ cell development Hormones-estrogen, progesterone and testosterone GHRH SS TRH Anterior Pituitary GROWTH TSH HORMONE Liver Other organs IGF-1 Growth Metabolism Thyroid Thyroxine T 3 PIH PROLACTIN Breasts Development Milk CRH ACTH Adrena l cortex Cortiso l Summary of Hypothalamic-anterior-pituitary system

Human Physiology Endocrine System

Human Physiology Endocrine System

Human Physiology Endocrine System