Basic Endocrin ology

1. Basic Endocrinology Prof. Dr.sc.agr. Ir. Suyadi, MS.

2. Endocrinology: • Endocrinology (from Greek ἔνδον, endo, "within"; κρῑνω, krīnō, "to separate"; and -λογία, -logia) is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones HORMONE

3. Endocrine vs exocrine • Endocrine: • Ductulless gland, secrets the chemical material  hormone  blood vessels • The hormone flow through the blood stream to the target organ • Targeted organ was stimulated and go to action • Exocrine: • Ductulled gland. Secrets the chemical material  enzyme, water+material, acid, • Secr material flow outside through spec lumen • Target organe or material are end target

4. 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

5. Sensing and signaling Endocrine “glands” synthesize and store hormones. These glands have a sensing and signaling system which regulate the duration and magnitude of hormone release via feedback from the target cell.

6. 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.

7. 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.

8. Hormones travel via the blood stream 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. Major hormones and systems • Top down organization of endocrine system. • Hypothalamus produces releasing factors that stimulate production of anterior pituitary hormone which act on peripheral endocrine gland to stimulate release of third hormone • Specific examples to follow • Posterior pituitary hormones are synthesized in neuronal cell bodies in the hypothalamus and are released via synapses in posterior pituitary. • Oxytocin and antidiuretic hormone (ADH)

14. Major Glands of the Endocrine system • Hypothalamus • Pituitary • Thyroid • Parathyroid • Adrenal. • Pancreas • Ovaries • Testes

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19. Pituitary gland • Master gland of body • Located in the depression of sphenoid bone • Produces many hormones that affect other glands • thyroid stimulating hormone • Somatotropin- growth hormone • Lutenizing (LH)- causes ovulation • ICSH- causes testes to secrete testosterone • Melanocyte stimulating- distribution of melanin in skin • ADH- antidiuretic hormone

20. Thyroid Hormone • Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms. • Thyroid hormone is produced by the thyroid gland and is lipid soluble • Thyroid hormones are produced by modification of a tyrosine residue contained in thyroglobulin, post-translationally modified to bind iodine, then proteolytically cleaved and released as T4 and T3. T3 and T4 then bind to thyroxin binding globulin for transport in the blood

21. Regulation of hormone secretion • Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are: ·        receipt of stimulus ·        synthesis and secretion of hormone ·        delivery of hormone to target cell ·        evoking target cell response ·        degradation of hormone

22. Control of Endocrine Activity • The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. • Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial.

23. Control of Endocrine Activity • The concentration of hormone as seen by target cells is determined by three factors: • Rate of production • Rate of delivery • Rate of degradation and elimination

24. Control of Endocrine Activity Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail.

25. Control of Endocrine Activity • Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow.

26. Control of Endocrine Activity • Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. • Shutting off secretion of a hormone that has a very short half-life causes circulating hormone concentration to plummet, but if a hormone's biological half-life is long, effective concentrations persist for some time after secretion ceases.

27. Feedback Control of Hormone Production Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion

28. Inputs to endocrine cells

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

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

31. 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

32. 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.

33. Circadian (chronotropic) control

34. Circadian Clock

35. Physiological importance of pulsatile hormone release • Demonstrated by GnRH infusion • If given once hourly, gonadotropin secretion and gonadal function are maintained normally • A slower frequency won’t maintain gonad function • Faster, or continuous infusion inhibits gonadotropin secretion and blocks gonadal steroid production

36. Clinical correlate • Long-acting GnRH analogs (such as leuproline) have been applied to the treatment of precocious puberty, to manipulate reproductive cycles (used in IVF), for the treatment of endometriosis, PCOS, uterine leiomyoma etc

37. Feedback control • Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion • Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation

38. Negative feedback effects of cortisol

39. Feedback control of insulin by glucose concentrations