1. Endocrine System: Overview Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus The pancreas and gonads produce both hormones and exocrine products The pancreas and gonads produce both hormones and exocrine products

2. Endocrine System: Overview The hypothalamus has both neural functions and releases hormones The hypothalamus has both neural functions and releases hormones Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

3. Major Endocrine Organs Figure 16.1

4. Autocrines and Paracrines Autocrines – chemicals that exert effects on the same cells that secrete them Autocrines – chemicals that exert effects on the same cells that secrete them Paracrines – locally acting chemicals that affect cells other than those that secrete them Paracrines – locally acting chemicals that affect cells other than those that secrete them These are not considered hormones since hormones are long-distance chemical signals These are not considered hormones since hormones are long-distance chemical signals

5. Hormones Hormones – chemical substances secreted by cells into the extracellular fluids Hormones – chemical substances secreted by cells into the extracellular fluids Regulate the metabolic function of other cells Regulate the metabolic function of other cells Have lag times ranging from seconds to hours Have lag times ranging from seconds to hours Tend to have prolonged effects Tend to have prolonged effects Are classified as amino acid-based hormones, or steroids Are classified as amino acid-based hormones, or steroids Eicosanoids – biologically active lipids with local hormone–like activity Eicosanoids – biologically active lipids with local hormone–like activity

6. Types of Hormones Amino acid based Amino acid based Amines, thyroxine, peptide, and protein hormones Amines, thyroxine, peptide, and protein hormones Steroids – gonadal and adrenocortical hormones, and hormones from the kidneys Steroids – gonadal and adrenocortical hormones, and hormones from the kidneys Remain in the blood stream longer because they are bound to proteins Remain in the blood stream longer because they are bound to proteins Eicosanoids – leukotrienes and prostaglandins Eicosanoids – leukotrienes and prostaglandins Are derived from lipids Are derived from lipids

7. Hormone Action Hormones alter target cell activity by one of two mechanisms Hormones alter target cell activity by one of two mechanisms Second messengers: Second messengers: Regulatory G proteins Regulatory G proteins Amino acid–based hormones Amino acid–based hormones Direct gene activation Direct gene activation Steroid hormones Steroid hormones The precise response depends on the type of the target cell The precise response depends on the type of the target cell

8. Mechanism of Hormone Action Hormones produce one or more of the following cellular changes in target cells Hormones produce one or more of the following cellular changes in target cells Alter plasma membrane permeability Alter plasma membrane permeability Stimulate protein synthesis Stimulate protein synthesis Activate or deactivate enzyme systems Activate or deactivate enzyme systems Induce secretory activity Induce secretory activity Stimulate mitosis Stimulate mitosis

9. Amino Acid-Based Hormone Action: cAMP Second Messenger Hormone (first messenger) binds to a receptor Hormone (first messenger) binds to a receptor Hormone binds to a G protein Hormone binds to a G protein The G protein is activated as it binds to GTP, which displaces GDP The G protein is activated as it binds to GTP, which displaces GDP Activated G protein activates the effector enzyme adenylate cyclase Activated G protein activates the effector enzyme adenylate cyclase Adenylate cyclase generates cAMP (second messenger) from existing ATP Adenylate cyclase generates cAMP (second messenger) from existing ATP cAMP activates protein kinases (cause cellular effects) cAMP activates protein kinases (cause cellular effects)

10. Receptor Hormone A Receptor GTP ATP cAMP Inactive protein kinase A Active protein kinase A Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channels, etc.) Adenylate cyclaseHormone B GDP Extracellular fluid Cytoplasm GsGs GiGi 1 2 3 4 32 1 5 Figure 16.2 Amino Acid-Based Hormone Action: cAMP Second Messenger

11. Hormone binds to the receptor and activates G protein Hormone binds to the receptor and activates G protein G protein binds and activates phospholipase G protein binds and activates phospholipase Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both are second messengers) Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both are second messengers) DAG activates protein kinases DAG activates protein kinases IP 3 triggers release of Ca 2+ stores IP 3 triggers release of Ca 2+ stores Ca 2+ (third messenger) alters responses at the cellular level Ca 2+ (third messenger) alters responses at the cellular level Amino Acid-Based Hormone Action: PIP-Calcium

12. GTP PIP 2 IP 3 Receptor GTP Catecholamines TRH ADH GnRH Oxytocin Triggers responses of target cell GDP Extracellular fluid Cytoplasm Inactive protein kinase C Active protein kinase C Phospholipase C GqGq Ca 2+ Ca 2+ - calmodulin Hormone Endoplasmic reticulum DAG 1 2 3 4 5 5 6 Figure 16.3 Amino Acid-Based Hormone Action: PIP Mechanism

13. Steroid Hormones This interaction prompts DNA transcription to produce mRNA This interaction prompts DNA transcription to produce mRNA The mRNA is translated into proteins, which bring about a cellular effect The mRNA is translated into proteins, which bring about a cellular effect

14. Steroid hormone Steroid hormone Cytoplasm Receptor- chaperonin complex Molecular chaperones Receptor-hormone complex Hormone response elements Binding Transcription Chromatin mRNA Nucleus New protein Translation Ribosome mRNA Figure 16.4

15. Steroid hormone Figure 16.4 Target Cell Specificity Hormones circulate to all tissues but only activate cells referred to as target cells Hormones circulate to all tissues but only activate cells referred to as target cells Target cells must have specific receptors to which the hormone binds Target cells must have specific receptors to which the hormone binds These receptors may be intracellular or located on the plasma membrane These receptors may be intracellular or located on the plasma membrane

16. Target Cell Specificity Examples of hormone activity Examples of hormone activity ACTH receptors are only found on certain cells of the adrenal cortex ACTH receptors are only found on certain cells of the adrenal cortex Thyroxin receptors are found on nearly all cells of the body Thyroxin receptors are found on nearly all cells of the body

17. Target Cell Activation Target cell activation depends on three factors Target cell activation depends on three factors Blood levels of the hormone Blood levels of the hormone Relative number of receptors on the target cell Relative number of receptors on the target cell The affinity of those receptors for the hormone The affinity of those receptors for the hormone Up-regulation – target cells form more receptors in response to less hormone Up-regulation – target cells form more receptors in response to less hormone Down-regulation – target cells lose receptors in response to more hormone Down-regulation – target cells lose receptors in response to more hormone

18. Hormone Concentrations in the Blood Hormones circulate in the blood in two forms – free or bound Hormones circulate in the blood in two forms – free or bound Steroids and thyroid hormone are attached to plasma proteins Steroids and thyroid hormone are attached to plasma proteins All others are unencumbered and can easily move out of the bloodstream to bind to the appropriate receptors All others are unencumbered and can easily move out of the bloodstream to bind to the appropriate receptors

19. Hormone Concentrations in the Blood Concentrations of circulating hormone reflect: Concentrations of circulating hormone reflect: Rate of release Rate of release Speed of inactivation and removal from the body Speed of inactivation and removal from the body Hormones are removed from the blood by: Hormones are removed from the blood by: Degrading enzymes in the plasma or interstitial fluid Degrading enzymes in the plasma or interstitial fluid The kidneys The kidneys Liver enzyme systems Liver enzyme systems

20. Interaction of Hormones at Target Cells Three types of hormone interaction Three types of hormone interaction Permissiveness – one hormone cannot exert its effects without another hormone being present Permissiveness – one hormone cannot exert its effects without another hormone being present Synergism – more than one hormone produces the same effects on a target cell Synergism – more than one hormone produces the same effects on a target cell Antagonism – one or more hormones opposes the action of another hormone Antagonism – one or more hormones opposes the action of another hormone

21. Control of Hormone Release Blood levels of hormones: Blood levels of hormones: Are controlled by negative feedback systems Are controlled by negative feedback systems Vary only within a narrow desirable range Vary only within a narrow desirable range Hormones are synthesized and released in response to: Hormones are synthesized and released in response to: Humoral stimuli Humoral stimuli Neural stimuli Neural stimuli Hormonal stimuli Hormonal stimuli

22. Humoral Stimuli Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients Example: concentration of calcium ions in the blood Example: concentration of calcium ions in the blood Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca 2+ concentrations to rise and the stimulus is removed PTH causes Ca 2+ concentrations to rise and the stimulus is removed

23. Humoral Stimuli Figure 16.5a

24. Neural Stimuli Neural stimuli – nerve fibers stimulate hormone release Neural stimuli – nerve fibers stimulate hormone release Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines Figure 16.5b

25. Hormonal Stimuli Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs The hypothalamic hormones stimulate the anterior pituitary The hypothalamic hormones stimulate the anterior pituitary In turn, pituitary hormones stimulate targets to secrete still more hormones In turn, pituitary hormones stimulate targets to secrete still more hormones

26. Hormonal Stimuli Figure 16.5c

27. Nervous System Modulation The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms

28. Nervous System Modulation The nervous system can override normal endocrine controls The nervous system can override normal endocrine controls For example, control of blood glucose levels For example, control of blood glucose levels Normally the endocrine system maintains blood glucose Normally the endocrine system maintains blood glucose Under stress, the body needs more glucose Under stress, the body needs more glucose The hypothalamus and the sympathetic nervous system are activated to supply ample glucose The hypothalamus and the sympathetic nervous system are activated to supply ample glucose

29. Major Endocrine Organs: Pituitary (Hypophysis) Pituitary gland – two-lobed organ that secretes nine major hormones Pituitary gland – two-lobed organ that secretes nine major hormones Neurohypophysis – posterior lobe (neural tissue) and the infundibulum Neurohypophysis – posterior lobe (neural tissue) and the infundibulum Receives, stores, and releases hormones from the hypothalamus Receives, stores, and releases hormones from the hypothalamus Adenohypophysis – anterior lobe, made up of glandular tissue Adenohypophysis – anterior lobe, made up of glandular tissue Synthesizes and secretes a number of hormones Synthesizes and secretes a number of hormones

30. Major Endocrine Organs: Pituitary (Hypophysis) Figure 16.6

31. Pituitary-Hypothalamic Relationships: Posterior Lobe The posterior lobe is a downgrowth of hypothalamic neural tissue The posterior lobe is a downgrowth of hypothalamic neural tissue Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract) Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract) Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH) Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH) These hormones are transported to the posterior pituitary These hormones are transported to the posterior pituitary

32. Pituitary-Hypothalamic Relationships: Anterior Lobe The anterior lobe of the pituitary is an outpocketing of the oral mucosa The anterior lobe of the pituitary is an outpocketing of the oral mucosa There is no direct neural contact with the hypothalamus There is no direct neural contact with the hypothalamus

33. There is a vascular connection, the hypophyseal portal system, consisting of: There is a vascular connection, the hypophyseal portal system, consisting of: The primary capillary plexus The primary capillary plexus The hypophyseal portal veins The hypophyseal portal veins The secondary capillary plexus The secondary capillary plexus Pituitary-Hypothalamic Relationships: Anterior Lobe

34. Adenophypophyseal Hormones The six hormones of the adenohypophysis: The six hormones of the adenohypophysis: Abbreviated as GH, TSH, ACTH, FSH, LH, and PRL Abbreviated as GH, TSH, ACTH, FSH, LH, and PRL Regulate the activity of other endocrine glands Regulate the activity of other endocrine glands In addition, pro-opiomelanocortin (POMC): In addition, pro-opiomelanocortin (POMC): Has been isolated from the pituitary Has been isolated from the pituitary Is split into ACTH, opiates, and MSH Is split into ACTH, opiates, and MSH

35. Activity of the Adenophypophysis The hypothalamus sends a chemical stimulus to the anterior pituitary The hypothalamus sends a chemical stimulus to the anterior pituitary Releasing hormones (RH) stimulate the synthesis and release of hormones Releasing hormones (RH) stimulate the synthesis and release of hormones Inhibiting hormones (IH) shut off the synthesis and release of hormones Inhibiting hormones (IH) shut off the synthesis and release of hormones Rate of secretion is controlled via negative feedback Rate of secretion is controlled via negative feedback

36. Activity of the Adenophypophysis The tropic hormones that are released are: The tropic hormones that are released are: Thyroid-stimulating hormone (TSH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Luteinizing hormone (LH)

37. Growth Hormone (GH) Produced by somatotropic cells of the anterior lobe that: Produced by somatotropic cells of the anterior lobe that: Stimulate most cells, but target bone and skeletal muscle Stimulate most cells, but target bone and skeletal muscle Promote protein synthesis and encourage the use of fats for fuel Promote protein synthesis and encourage the use of fats for fuel Most effects are mediated indirectly by somatomedins Most effects are mediated indirectly by somatomedins

38. Growth Hormone (GH) Antagonistic hypothalamic hormones regulate GH Antagonistic hypothalamic hormones regulate GH Growth hormone–releasing hormone (GHRH) stimulates GH release Growth hormone–releasing hormone (GHRH) stimulates GH release Growth hormone–inhibiting hormone (GHIH) inhibits GH release Growth hormone–inhibiting hormone (GHIH) inhibits GH release

39. Metabolic Action of Growth Hormone GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors Direct action promotes lipolysis and inhibits glucose uptake Direct action promotes lipolysis and inhibits glucose uptake

40. Metabolic Action of Growth Hormone (GH) Figure 16.7

41. Thyroid Stimulating Hormone (Thyrotropin) Stimulates the normal development and secretory activity of the thyroid Stimulates the normal development and secretory activity of the thyroid Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH) Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH) Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

42. Adrenocorticotropic Hormone (Corticotropin) Stimulates the adrenal cortex to release corticosteroids Stimulates the adrenal cortex to release corticosteroids Triggered by hypothalamic corticotropin- releasing hormone (CRH) in a daily rhythm Triggered by hypothalamic corticotropin- releasing hormone (CRH) in a daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH

43. Gonadotropins Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Regulate the function of the ovaries and testes Regulate the function of the ovaries and testes FSH stimulates gamete (egg or sperm) production FSH stimulates gamete (egg or sperm) production Absent from the blood in prepubertal boys and girls Absent from the blood in prepubertal boys and girls Triggered by the hypothalamic gonadotropin- releasing hormone (GnRH) during and after puberty Triggered by the hypothalamic gonadotropin- releasing hormone (GnRH) during and after puberty

44. Functions of Gonadotropins In females In females LH works with FSH to cause maturation of the ovarian follicle LH works with FSH to cause maturation of the ovarian follicle LH works alone to trigger ovulation (expulsion of the egg from the follicle) LH works alone to trigger ovulation (expulsion of the egg from the follicle) LH promotes synthesis and release of estrogens and progesterone LH promotes synthesis and release of estrogens and progesterone

45. Functions of Gonadotropins In males In males LH stimulates interstitial cells of the testes to produce testosterone LH stimulates interstitial cells of the testes to produce testosterone LH is also referred to as interstitial cell-stimulating hormone (ICSH) LH is also referred to as interstitial cell-stimulating hormone (ICSH)

46. Prolactin (PRL) In females, stimulates milk production by the breasts In females, stimulates milk production by the breasts Triggered by the hypothalamic prolactin- releasing hormone (PRH) Triggered by the hypothalamic prolactin- releasing hormone (PRH) Inhibited by prolactin-inhibiting hormone (PIH) Inhibited by prolactin-inhibiting hormone (PIH) Blood levels rise toward the end of pregnancy Blood levels rise toward the end of pregnancy Suckling stimulates PRH release and encourages continued milk production Suckling stimulates PRH release and encourages continued milk production

47. The Posterior Pituitary and Hypothalamic Hormones Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocin Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocin ADH and oxytocin are synthesized in the hypothalamus ADH and oxytocin are synthesized in the hypothalamus ADH influences water balance ADH influences water balance Oxytocin stimulates smooth muscle contraction in breasts and uterus Oxytocin stimulates smooth muscle contraction in breasts and uterus Both use PIP-calcium second-messenger mechanism Both use PIP-calcium second-messenger mechanism