Hypothalamic Control of the Pituitary Gland/Pituitary hormone function Flashcards Preview

My DEMS 4 > Hypothalamic Control of the Pituitary Gland/Pituitary hormone function > Flashcards

Flashcards in Hypothalamic Control of the Pituitary Gland/Pituitary hormone function Deck (34):
1

Connection between anterior pituitary and hypothalamus

Hypothalamo-hypophyseal portal system
-blood enters median eminence thru superior hypophyseal arteries
-Nerve terminal into capillary plexus, neurohormones released into cap bed and transported via portal system to second capillary plexus in anterior lobe

-Plexus outside BBB
-Hormones reach anterior lobe basically undiluted

2

Structure of hypothalamic hormones

-peptides (except for dopamine, a catecholamine)

3

origin of posterior pituitary

posterior: invagination of hypothalamus

anterior: from pharyngeal epithelium (Rathke's pouch)

4

TRH: thyrotropin releasing hormone

Hypothalamic hormone
tripeptide
Acts on thyrotrophs
Associated anterior pituitary hormone:
increases TSH
increases PRL

Gs

5

Gonadotropin releasing hormone (GnRH)

hypothalamic hormone
decapeptide
-acts on gonadotrophs
Associated anterior pituitary hormone:
increases LH
increases FSH

Gq

6

Corticoptropin releasing hormone (CRH)

hypothalamic hormone
41 aa
Acts on corticotrophs

Associated anterior pituitary hormone:
increases POMC
increases ACTH (a derivative of POMC)

Gs

7

Growth hormone releasing factor (GHRH)

14 amino acids
Acts on somatotrophs
Associated anterior pituitary hormone:
increases GH

8

Somatostatin (GIH)

14 aa
Acts on somatotrophs
Associated anterior pituitary hormone:
decreases GH
decreases TSH

Gi

9

Prolactin inhibiting hormone (PIH)

-Thought to be Dopamine
Acts on lactotrophs
Associated anterior pituitary hormone:
decreases PRL

Gi

10

Hormone secretion from hypothalamic neurons

-Many inputs from thalamus, limbic system, sleep vs wake, light, etc
-Calcium dependent release

11

Prolactin

-produced by lactotrophs in anterior pituitary (Ca dependent release)
-protein hormone released into blood stream
-carried mostly free, fraction bound to carrier proteins (t1/2 of 20-30 mins.)
-Cytokine receptor family
(two binding sites for 2 molecules of prolactin)
-When bound, Janus kinase (a tyr kinase) is activated, receptor stabilized, activates downstream STATs
-modulate transcription
(JAK/STAT pathway)
-Main action: on mammary gland

12

Mammary gland function

1. lactogenesis (milk production)
2. galactopoiesis
3. Mammogenesis (growth of gland itself)

Prolactin facilitates all three processes.

Prolactin also inhibits pulsatile secretion of GnRH by hypothalamic neurons and thus inhibits pregnancy.

13

regulators of prolactin

-Prolactin under tonic negative control thru dopamine (dopamine acts on lactotrophs to inhibit prolactin)
-Stimulation of prolactin by TRH (thyrotropin releasing hormone)

-estrogen and progesterone: positive effect on mammogenesis, but inhibit milk production (lactogenesis, galactopoiesis)

14

hyperproduction of prolactin

hyperprolactinemia
-lactotroph tumor
-D2 antagonists

Common sx:
1. Galactorrhea
2. amenorrhea
3. loss of libido

15

Hypoprolactinemia

Rarer than hyper-

Sheehan's Syndrome:
Destruction of pituitary itself (can have hemorrhagic destruction of pituitary during childbirth)
-immediately notice failure to lactate

16

Growth hormone

-released from somatotrophs of anterior pituitary
-release promoted by GHRH, inhibited by somatostatin
-JAK/STAT pathway once it reaches receptor

-Metabolic actions:
GH provides body with enough energy resources to utilize for growth.
-GH increases gluconeogenesis, promotes glycogenolysis, counters insulin actions
-Thus GH is diabetogenic in excess amounts.
-GH drives aa into skeletal muscle, protein synthesis increased (so protein spared)
-GH increases FFA, lipolysis (hormone sensitive lipase)
-Liver: increased RNA, protein, glucose synthesis. IGF-1 secreted, mediates indirect effects. (Glucose increase mainly due to gluconeogenesis)

17

Growth effects of GH

-mediated by IGF (insulin-like growth hormone) (produced in liver and other places upon action of GH)
-GH + insulin leads to IGF

IGF acts on EGF family of receptors (similar to insulin)
-IGF receptors activate insulin receptor associated proteins 1 and 2 (IRS I and II), can then activate MAP kinase or PI-3 kinase pathways

GH actions mediated by IGF-1:
IGF promotes long bone growth (pre-puberty)
Promotes appositional growth

Muslce: stimulates proliferation, diff, protein synthesis

Adipose tissue: stimulates uptake of glucose and inhibits lypolysis (antagonizes action of GH)

IGF-1 is predominant form postnatally (more than IGF-2):

18

GH release regulation

GHRH promotes GH release
Somatostatin inhibits release of GH

Both from hypothalamus

amino acids (arginine), low FFA, alpha adrenergic agonists (clonidine), beta adrenergic antagonists (propranolol), and estrogens potentiate release of GHRH

Hypoglycemia promotes GHRH (GH) release
Hyperglycemia , high FFA, obesity, alpha adrenergic antagonists and beta adrenergic agonists, and pharm doses of corticosteroids inhibit GH secretion

Some GH is bound to GHBP.

19

Normal human growth

-intake aa and glucose
-aa leads to GH release
-glucose leads to insulin release
-GH + insulin leads to IGF

20

Starvation and GH

low aa and low glucose
-low glucose leads to GH release
-low glucose means low insulin and no IGF

21

Hyperfunction of growth hormone (Excess production)

-prior to puberty? pronounced linear growth (Gigantism)
-increased GH (diabetes), increased IGF

After puberty?
-increased appositional growth (Acromegaly)
-less drastic consequences than gigantism

22

Hypofunction of growth hormone

-Dwarfism (failure of linear growth)
-Laron's dwarfism (response to GH lacking, not GH itself)
-African pigmy (decreased IGF response)

-Deficiency of GH not as severe or life threatening as hyperfunction before puberty

23

CRH and GHRH are coupled to

Gs (stim adenylate cyclase to produce cAMP in corticotrophs (CRH) and somatotrophs (GHRH))

24

somatatostatin coupled to

Gi
-decreased cAMP

(DA also leads to reduced cAMP in lactotrophs)

25

GnRH receptor activation

-in gonadotrophs leads to hydrolysis of membrane phosphatidyl inositol

26

AP hormone release ids dependent on

Ca
-but evidence exists for several intracellular cascades in various pituitary cells.
-membrane conductances play a role too

27

How is pituitary attached to hypothalamus

pituitary stalk

28

adenohypophysis

-anterior pituitary:
comprised of pars tuberalis, pars intermedia, and the pars distalis (anterior lobe)
hormones of AP secreted from anterior lobe

29

PRF

?TRH
-from lactotrophs
-increases prolactin
-polypeptide

30

Release of hormones from AP (timing)

-pulsatile
-my be due to pulsatile secretion of the stimulating/inhibiting hypothalamic hormone

31

Neurohypophysis

posterior pituitary
-from evagination of diencephalon (direct connection to hypothalamus)
-median eminence, infundibular stem, infundibular process (pars nervosa)
-Posterior pituitary hormones are synthesized in hypothalamus in two nuclei:
1. supraoptic nucleus
2. paraventricular nucleus
Nuclei have two cell types:
1. magnocellular neurons (processes extend into post pit ending in pars nervosa)
2. parvocellular neurons: end in median eminence (so some like ADH can act on AP)

Post pit secretes ADH and oxytocin (nonapeptides). From prohormone in hypothal (cleaved into hormone and protein neurophysin)
-Ca dependent release

32

ADH

-or "vasopressin"
secreted in response to increase in plasma osmolarity or a decrease in blood pressure.
-acts on renal tubule and collecting ducts (conserve water)
V1 coupled to Gq and PLC pathway (vasopressive action of ADH)
V2 coupled to Gs and cAMP, regulates effects of ADH on GFR.

33

Oxytocin: when is it secreted?

1. during passage of infant through cervix at childbirth
2. during sexual intercourse
3. in response to suckling infant in breast feeding.

Oxytocin acts on uterus to cause contraction of myometrium.
During lactation: contraction of myoepithelial cells (milk ejection)

34

Assessing GH levels and secretion

-check several times over a day
-stimulation by exercise or high doses of arginine often used to asses GH status
-IGF-1 levels is helpful too (less diurnal variation)