part ii target cell speciﬁcity - wckleinelp• the nervous system modiﬁes the smulaon of...

5/20/08

1

Part II

Target Cell Specificity

Target Cell Specificity

•  Examples of hormone ac@vity – ACTH receptors are only found on certain cells of the adrenal cortex

– Thyroxin receptors are found on nearly all cells of the body

5/20/08

2

Target Cell Ac@va@on

•  Target cell ac@va@on depends on three factors –  Blood levels of the hormone –  Rela@ve number of receptors on the target cell

–  The affinity of those receptors for the hormone

•  Up‐regula@on – target cells form more receptors in response to the hormone

•  Down‐regula@on – target cells lose receptors in response to the hormone

Hormone Concentra@ons in the Blood

•  Hormones circulate in the blood in two forms – free or bound – Steroids and thyroid hormone are aOached to plasma proteins

– All others are unencumbered

Hormone Concentra@ons in the Blood

•  Concentra@ons of circula@ng hormone reflect: – Rate of release – Speed of inac@va@on and removal from the body

•  Hormones are removed from the blood by: – Degrading enzymes – The kidneys – Liver enzyme systems

5/20/08

3

Interac@on of Hormones at Target Cells

•  Three types of hormone interac@on – 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

– Antagonism – one or more hormones opposes the ac@on of another hormone

– Neuronal – hormonal release via acXon poten@als and neurosecretory transduc@on

– Humoral – self‐monitoring detc@on and release via specific gland, i.e pancreas and parathyroid

Control of Hormone Release

•  Blood levels of hormones: – Are controlled by nega@ve feedback systems – Vary only within a narrow desirable range

•  Hormones are synthesized and released in response to: – Humoral s@muli – Neural s@muli – Hormonal s@muli

Humoral S@muli

•  Humoral s@muli – secre@on of hormones in direct response to changing blood levels of ions and nutrients

•  Example: concentra@on of calcium ions in the blood – Declining blood Ca2+ concentra@on s@mulates the parathyroid glands to secrete PTH (parathyroid hormone)

– PTH causes Ca2+ concentra@ons to rise and the s@mulus is removed

5/20/08

4

Humoral S@muli

Figure 16.5a

Neural S@muli

•  Neural s@muli – nerve fibers s@mulate hormone release – Preganglionic sympathe@c nervous system (SNS) fibers s@mulate the adrenal medulla to secrete catecholamines

Figure 16.5b

Hormonal S@muli

•  Hormonal s@muli – release of hormones in response to hormones produced by other endocrine organs – The hypothalamic hormones s@mulate the anterior pituitary

–  In turn, pituitary hormones s@mulate targets to secrete s@ll more hormones

5/20/08

5

Hormonal S@muli

Figure 16.5c

Nervous System Modula@on

•  The nervous system modifies the s@mula@on of endocrine glands and their nega@ve feedback mechanisms

Nervous System Modula@on

•  The nervous system can override normal endocrine controls – For example, control of blood glucose levels

•  Normally the endocrine system maintains blood glucose

•  Under stress, the body needs more glucose

•  The hypothalamus and the sympathe@c nervous system are ac@vated to supply ample glucose

5/20/08

6

Major Endocrine Organs: Pituitary (Hypophysis)

•  Pituitary gland – two‐lobed organ that secretes nine major hormones

•  Neurohypophysis – posterior lobe (neural @ssue) and the infundibulum – Receives, stores, and releases hormones from the hypothalamus

•  Adenohypophysis – anterior lobe, made up of glandular @ssue – Synthesizes and secretes a number of hormones

Major Endocrine Organs: Pituitary (Hypophysis)

Figure 16.6

The Posterior Pituitary and Hypothalamic Hormones

•  Posterior pituitary – made of axons of hypothalamic neurons, stores an@diure@c hormone (ADH) and oxytocin

•  ADH and oxytocin are synthesized in the hypothalamus

•  ADH influences water balance •  Oxytocin s@mulates smooth muscle contrac@on in breasts and uterus

•  Both use PIP‐calcium second‐messenger mechanism

5/20/08

7

Oxytocin

•  Oxytocin is a strong s@mulant of uterine contrac@on

•  Regulated by a posi@ve feedback mechanism to oxytocin in the blood

•  Detected by the paraventricular nuclei of hypothalamus

•  This leads to increased intensity of uterine contrac@ons, ending in birth

•  Oxytocin triggers milk ejec@on (“letdown” reflex) in women producing milk

Decreased oxytocin in bloodstream

Detec@on by hypothalamic paraventricular

nuclei

Ac@on poten@als down

hypothalamuc‐hypophyseal tract

Neurosecretory transduc@on

Release of oxytocin at

neurpohypophysis

Targets smooth muscle of uterus

and myoepithelium of mammary glands

Contrac@on of smooth muscle +

Oxytocin

•  Synthe@c and natural oxytocic drugs are used to induce or hasten labor

•  Plays a role in sexual arousal and sa@sfac@on in males and nonlacta@ng females

5/20/08

8

An@diure@c Hormone (ADH)

•  ADH helps to avoid dehydra@on or water overload – Prevents urine forma@on

•  Osmoreceptors monitor the solute concentra@on of the blood

•  With high solutes, ADH preserves water

•  With low solutes, ADH is not released, thus causing water loss

•  Alcohol inhibits ADH release and causes copious urine output

Osmoreceptors in Supraop@c nuclei of hypothalamus detect low serum water levels

Ac@on poten@als sent to hypothalamic‐hypophyseal tracts

Release of vasopressin ADH at posterior

pituitary

Vasopressin acts as vasopressor of vascular

smooth muscle

ADH targets DCT of kidney tubules • Response to increase WATER reabsorp@on

Decrease in serum water

levels

Increases release of vasopressn

ADH

5/20/08

9

Vasopressin‐ADH

Targets vascular smooth muscle

vasoconstric@on

Decrease diameter mimics increased volume hence

increased pressure

Targets DCT of kidney tubules

Reabsorp@on of water

Increased vascular water volume

Increased pressure

Pituitary‐Hypothalamic Rela@onships: Posterior Lobe

•  The posterior lobe is a downgrowth of hypothalamic neural @ssue

•  Has a neural connec@on with the hypothalamus (hypothalamic‐hypophyseal tract)

•  Nuclei of the hypothalamus synthesize oxytocin and an@diure@c hormone (ADH)

•  These hormones are transported to the posterior pituitary

Pituitary‐Hypothalamic Rela@onships: Anterior Lobe

•  The anterior lobe of the pituitary is an outpocke@ng of the oral mucosa

•  There is no direct neural contact with the hypothalamus

5/20/08

10


•  There is a vascular connec@on, the hypophyseal portal system, consis@ng of: – The primary capillary plexus – The hypophyseal portal veins – The secondary capillary plexus

PLAY InterActive Physiology ®: The Hypothalamic Pituitary Axis


Figure 16.6

Adenophypophyseal Hormones

•  The six hormones of the adenohypophysis: – Abbreviated as GH, TSH, ACTH, FSH, LH, and PRL

– Regulate the ac@vity of other endocrine glands •  In addi@on, pro‐opiomelanocor@n (POMC):

– Has been isolated from the pituitary –  Is split into ACTH, opiates, and MSH

5/20/08

11

Anterior Pituitary Hormones

HORMONE TARGET RELEASING FACTOR

Thyrotropic Stimulating Hormone (TSH) Thyroid Glands TSHRF, TRH

Adrenocorticotropic Hormone (ACTH) Adrenal Glands ACTHRF; CRH

Follicle Stimulating Hormone (FSH)

Females - ovaries Males - testes FSHRF; GnRH

Leutinizing Hormone (LH)

Females - ovaries Males - testes LHRF; GnRH

Prolactin (PRL) Breast secretory tissue PRH; PIH (dopamine)

Melanocyte Stimulating Hormone (MSH) melanocytes -

Growth Hormones (GH) Liver, muscle, bones, cartilage and other tissues

GHRH;GHIH

Ac@vity of the Adenophypophysis

•  The hypothalamus sends a chemical s@mulus to the anterior pituitary – Releasing hormones s@mulate the synthesis and release of hormones

–  Inhibi@ng hormones shut off the synthesis and release of hormones

Ac@vity of the Adenophypophysis

•  The tropic hormones that are released are: – Thyroid‐s@mula@ng hormone (TSH)

– Adrenocor@cotropic hormone (ACTH) – Follicle‐s@mula@ng hormone (FSH) – Luteinizing hormone (LH)

5/20/08

12

Growth Hormone (GH)

•  Produced by somatotropic cells of the anterior lobe that: – S@mulate most cells, but target bone and skeletal muscle

– Promote protein synthesis and encourage the use of fats for fuel

•  Most effects are mediated indirectly by somatomedins

Growth Hormone (GH)

•  Antagonis@c hypothalamic hormones regulate GH – Growth hormone–releasing hormone (GHRH) s@mulates GH release

– Growth hormone–inhibi@ng hormone (GHIH) inhibits GH release

Metabolic Ac@on of Growth Hormone

•  GH s@mulates liver, skeletal muscle, bone, and car@lage to produce insulin‐like growth factors

•  Direct ac@on promotes lipolysis and inhibits glucose uptake

5/20/08

13

Metabolic Ac@on of Growth Hormone (GH)

Figure 16.7

Thyroid S@mula@ng Hormone (Thyrotropin)

•  S@mulates the normal development and secretory ac@vity of the thyroid

•  Triggered by hypothalamic pep@de thyrotropin‐releasing hormone (TRH)

•  Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH

Adrenocor@cotropic Hormone (Cor@cotropin)

•  S@mulates the adrenal cortex to release cor@costeroids

•  Triggered by hypothalamic cor@cotropin‐releasing hormone (CRH) in a daily rhythm

•  Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH

5/20/08

14

Gonadotropins

•  Gonadotropins – follicle‐s@mula@ng hormone (FSH) and luteinizing hormone (LH) – Regulate the func@on of the ovaries and testes – FSH s@mulates gamete (egg or sperm) produc@on

– Absent from the blood in prepubertal boys and girls

– Triggered by the hypothalamic gonadotropin‐releasing hormone (GnRH) during and aler puberty

Func@ons of Gonadotropins

•  In females – LH works with FSH to cause matura@on of the ovarian follicle

– LH works alone to trigger ovula@on (expulsion of the egg from the follicle)

– LH promotes synthesis and release of estrogens and progesterone

Func@ons of Gonadotropins

•  In males – LH s@mulates inters@@al cells of the testes to produce testosterone

– LH is also referred to as inters@@al cell‐s@mula@ng hormone (ICSH)

5/20/08

15

Prolac@n (PRL)

•  In females, s@mulates milk produc@on by the breasts

•  Triggered by the hypothalamic prolac@n‐releasing hormone (PRH)

•  Inhibited by prolac@n‐inhibi@ng hormone (PIH)

•  Blood levels rise toward the end of pregnancy

•  Suckling s@mulates PRH release and encourages con@nued milk produc@on

Thyroid Gland •  The largest endocrine gland, located in the anterior neck, consists of two lateral lobes connected by a median @ssue mass called the isthmus

•  Composed of follicles that produce the glycoprotein thyroglobulin

•  Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone

•  Other endocrine cells, the parafollicular cells, produce the hormone calcitonin

Thyroid Gland

Figure 16.8

5/20/08

16

•  Thyroid hormone – major metabolic hormone

•  Consists of two related iodine‐containing compounds – T4 – thyroxine; has two tyrosine molecules plus four bound iodine atoms

– T3 – triiodothyronine; has two tyrosines with three bound iodine atoms

Thyroid Hormone

Effects of Thyroid Hormone •  TH is concerned with:

– Glucose oxida@on –  Increasing metabolic rate – Heat produc@on

•  TH plays a role in: – Maintaining blood pressure – Regula@ng @ssue growth – Developing skeletal and nervous systems – Matura@on and reproduc@ve capabili@es

Synthesis of Thyroid Hormone •  Thyroglobulin is synthesized and discharged into the lumen

•  Iodides (I–) are ac@vely taken into the cell, oxidized to iodine (I2), and released into the lumen

•  Iodine aOaches to tyrosine, mediated by peroxidase enzymes, forming T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or DIT)

5/20/08

17

Synthesis of Thyroid Hormone

•  Iodinated tyrosines link together to form T3 and T4

•  Colloid is then endocytosed and combined with a lysosome, where T3 and T4 are cleaved and diffuse into the bloodstream

Figure 16.9

Iodine

T4

T4

T4

T3

T3

T3

T3 T4

Lysosome

Capillary

Iodide (I–)

Thyroid follicle cell

Colloid in lumen of follicle

To peripheral 9ssues

T4

T3

Lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid and hormones diffuse from follicle cell into bloodstream

Thyroglobulin colloid is endocytosed and combined with a lysosome

Iodinated tyrosines are linked together to form T3 and T4

Thyroglobulin colloid

Iodine is aCached to tyrosine in colloid, forming DIT and MIT

Thyroglobulin is synthesized and discharged into the follicle lumen

Iodide (I–) is trapped (ac9vely transported in) DIT (T2) MIT (T1)

Colloid

Golgi apparatus Rough ER

Iodide is oxidized to iodine

1

2 3a

5

6

3b

4

Figure 16.9

Capillary

Iodide (I–)



Thyroglobulin is synthesized and discharged into the follicle lumen Colloid


1

5/20/08

18

Figure 16.9

Capillary

Iodide (I–)




Iodide (I–) is trapped (ac9vely transported in)

Colloid


1

2

Figure 16.9

Iodine

Capillary

Iodide (I–)




Iodide (I–) is trapped (ac9vely transported in)

Colloid



1

2 3a

Figure 16.9

Iodine

Capillary

Iodide (I–)







Colloid



1

2 3a

3b

5/20/08

19

Figure 16.9

Iodine

Capillary

Iodide (I–)



T4

T3






Colloid



1

2 3a

3b

4

Figure 16.9

Iodine

T3 T4

Lysosome

Capillary

Iodide (I–)



T4

T3







Colloid



1

2 3a

5

3b

4

Figure 16.9

Iodine

T4

T4

T4

T3

T3

T3

T3 T4

Lysosome

Capillary

Iodide (I–)



To peripheral 9ssues

T4

T3

Lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid and hormones diffuse from follicle cell into bloodstream







Colloid



1

2 3a

5

6

3b

4

part ii target cell speciﬁcity - wckleinelp• the nervous system modiﬁes the smulaon of...

Documents