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Flashcards in Lecture 3 & 6 Deck (23):
1

Describe the structure of pituitary gland how the 2 lobes are morphologically derived and the clinical significance of the structures lying in close apposition to gland

Anterior lobe: oral ectoderm; outpouching of roof of pharynx called Rathke's pouch
Posterior lobe: neural tissue, embryonic forebrain

Clinical significance:
- whip lash may sever the pituitary stalk that passes through narrow opening in sellae turcica, to connect hypothalamus to pituitary
- optic chiasm lies on diaphragm between anterior clinoid process; tumor could cause blindness

2

Describe the blood supply to the both pituitary lobes and their clinical importance in effecting hormonal effects

The anterior pituitary gland and median eminence: superior hypophyseal artery (a branch of the internal carotid artery)
- allows delivery of increased hormones to anterior pituitary from hypothalamus

posterior pituitary and stalk: inferior and middle hypophyseal arteries

short plexus connects anterior and posterior lobes

3

Describe the relationship between anterior pituitary lobe and the hypothalamus, and the factors that cause release of hypothalamic hormones

anterior pituitary connected to hypothalamus via portal system

parvocellular neurons --> axon transport -> median eminence/hypothalamus --> portal system --> anterior pituitary

Factors causing hormone release:
sleep/wake cycle, temperature, other hormones, stress, and negative feedback

4

Identify appropriate hypothalamic factors that control the secretion of each of the anterior pituitary hormones

CRH: ACTH
TRH: TSH
GnRH: FSH & LH
GHRH: GH
GHIH: inhibition of GH
PIF: inhibition of PRL

5

Describe how different cell types that secrete different hormones and significance of their location with respect to structural lesions and describe 3 major families of the anterior pituitary hormones and their biosynthetic and structural structural similarity to similar class and placental hormones.

POSTEROLATERAL:
- gonadotrophs: LH & FSH
- somatotrophs: GH

ANTEROMEDIAL:
- corticotrophs: ACTH
- thyrotrophs: TSH

SCATTERED THROUGHOUT:
- lactotrophs: PRL

3 Classes of AP Hormones:
1. Glycoproteins: TSH, FSH, LH, hCG (identical alpha chains)
2. POMC (pro-opiomelanocortin)
3. Lactogens: GH, PRL, hPL

6

Understand negative feedback control of anterior pituitary hormone secretion at multiple level

response of target organ and endocrine negatively feedback to both anterior pituitary and hypothalamus

7

Describe growth hormone, which 2nd messenger it activates and what triggers its release.

GHRH is synthesized by hypothalamus to trigger the synthesis of GH in the anterior pituitary. GH is released in the presence of Ghrelin, which is released due to hypoglycemia.

GH binds to surface receptor that consequentially activates tyrosine kinase (JAK2). Activation of JAK2 initiates changes in the phosphorylation pattern of
cytoplasmic and nuclear proteins, ultimately stimulating the transcription of specific genes, including that for IGF-I.

8

Describe the effects of GHRH and somatostatin on GH release and their mechanism of action on target using which 2nd messenger.

GHRH binds to surface receptor, activating adenylyl cyclase, which releases the 2nd messenger, cAMP. Increased Ca2+ levels triggers exocytosis of GH and DNA transcription of GH

Somatostatin (aka GHIH) binds to surface receptor, inhibiting GPCR, therefore decreasing cAMP levels and inhibiting exocytosis.

9

Understand the pattern of secretion of growth hormone

Growth hormone has a pulsatile secretion with maximal peaks at night during stage 3 & 4 of slow wave, deep sleep.

GH levels are highest during adolescent, with its maximal peak at puberty.

10

Describe the metabolic and growth promoting actions of growth hormone. Describe their mechanism of action on target organs

REGULATION OF:
- skeletal and soft tissue growth
- carb, lipid, and protein metabolism (overall increase of blood glucose - diabetogenic)

MECHANISM OF ACTION
Direct:
- liver: glycogenolysis, IGF & IGF-BP synthesis
- adipose tissue: lipolysis and decreased glucose uptake
- muscle: increase AA uptake and protein synthesis and decreased glucose uptake

Indirect: Skeletal & extraskeletal
- IGF1 (somatomedin C): bind TK receptor of target cell membranes. Promotes linear bone growth, cartilage formation, protein synthesis, and increased organ size (cell growth and proliferation) and function.

- IGF BP (binding protein) increases half life

11

Describe the relationship between
growth hormone and the insulin-like growth factors and their binding proteins in the regulation of growth.

GH triggers the increases insulin secretion, whose usual physiologic mechanism of increasing glucose uptake is inhibited by increased FFA.

IGF (insulin-like growth factor)/somatomedin: structurally similar to pro-insulin; binds to TK receptors of target membranes. IGF BP increased half life in blood.

insufficent synthesis of IGF = dwarfism (African pygmies & Levi Loran)

12

Describe the effects of too much or too little of the Growth hormone

Increased GH = gigantism or acromegaly/diabetes (if after fusion of epiphyseal plates)

Decreased GH (panhypopituitarism) = due to lack of GH or resistance to GH, results in dwarfism (children); no known effects in adults

13

Describe the feedback mechanisms In regulation of growth hormone levels and what other factors affect growth

3 mechanisms:
1. GHRH
2. Somatostatin
3. IGF-1

* thyroid hormone has permissive action of GH

14

Describe the effects of loss of all pituitary hormones and effects of injury to pituitary stalk.

Panhypopituitarism: deficiency of all pituitary hormones
- 3 major effects:
1. hypothyroidism
2. decreased glucocorticoids (cortisol)
3. decreased androgens (sexual hormones)

Injury to pituitary stalk:
- results in:
1. diabetes insipidus
2. panhypopituitarism
3. HYPERLACTINEMIA

- Example: Sheehan's syndrome due to postpartum hemorrhage

15

Describe the chemical nature, synthesis and release of prolactin

***TONICALLY INHIBITED BY DOPAMINE (PIF)

SYNTHESIS:
- produced in Anterior Pituitary and stored in granules

MAJOR FUNCTION:
- breast development
- milk production (initiates and maintains)
- inhibition of ovulation in lactating women via GnRH suppression

MECHANISM OF ACTION:
- GPCR (dopamine acts on Gi to decrease cAMP, decreasing PKA, and Ca2+, which inhibits the release of PRL from lactotroph)
- At target tissue: PRL activated TK resulting in modulation of gene expression leading to prolactin effects (breast differentiation, duct proliferation and branching, glandular tissue development, milk protein synthesis, lactogenic enzyme synthesis, mammary gland development, and milk production)

16

Explain the mechanism of action of prolactin at its target cells and its physiologic actions and functions

At target tissue: PRL activated TK resulting in modulation of gene expression leading to prolactin effects (breast differentiation, duct proliferation and branching, glandular tissue development, milk protein synthesis, lactogenic enzyme synthesis, mammary gland development, and milk production)

***secretion of prolactin negatively feeds back causing dopamine release to increase and inhibit further secretion of prolactin***

17

Describe symptoms of prolactinomas and prolactin imbalance

Symptoms of excess:
- galatorrhea
- decreased libido
- decreased ovulation and spermatogenesis (inhibition of GnRH)

Treatment: bromocriptine, dopamine agonist to treat excessive prolactin

Symptoms of deficieny:
- failure to lactate

18

Describe posterior pituitary hormones and their structural similarity

- Neuro-endocrine secretion
- 9 AA peptides, with minor differences
- synthesized from prohormone containing neurohypophysins

Note: diabete insipidus associated with mutation of neurohypophysins

19

Describe the stimuli and mechanisms that control vasopressin secretion

STIMULI:
1. decreased ECF volume (baroreceptors)
2. increased ECF osmolarity (osmoreceptors)

MECHANISM:

In kidney: principal cell
- V2 receptor increased cAMP (Gs)
- exocytosis of AQP2 channels in vesicles
- increased production of AQP2

In BV:
- V1 receptor increased IP3 & DAG (Gq)
- increased Ca2+ levels
- contraction of vascular smooth muscle

20

List the target cells for vasopressin and explain why vasopressin is also
known as antidiuretic hormone.

Target cells of Vasopressin:
- principal cells: acts to increase water reabsorption (anti-diuretic hormone)
- BV smooth muscle: vasoconstriction of arterioles, resulting in increased arterial pressure

21

Identify disease states caused by a) over secretion, and b) under secretion of vasopressin and list the principle symptoms of each

A. Over secretion: SIADH (syndrome of inappropriate ADH)
- secretion of ADH due to tumor (i.e. oat cell carcinoma)

Symptoms:
- increased ADH secretion and water retention
- increased urinary concentration
- decreased serum osmolarity

B. Under secretion: Diabetes Insipidus:
- 3 types:
1. Psychogenic: uncontrollable intake of water

2. Central: inability to secrete ADH

3. Nephrogenic: insensitivity or resistance of receptors to ADH

Differential: Central DI will present with low levels of ADH, while nephrogenic DI will present with high levels of ADH

22

Name the stimuli for oxytocin release in relation to its reproductive and lactation functions.

STIMULI: (positive feedback)
1. pressure against cervix
2. nursing baby

23

List the target organs and functional effects of oxytocin.

MECHANISM:
Target tissue: cervix and myoepithelial cells of breast
- binds to Gq receptor
- increase of IP3 & DAG
- increased Ca2+ levels
- contraction of smooth muscle