4. Endocrine Pathology II Flashcards
Hypothalamus
• Main controller of pituitary secretions.
• Hypothalamic regulatory hormones:
• Releasing hormones (RH):
• Stimulate synthesis and secretion of hormones from ____.
• Inhibiting hormones (IH):
• Prevent synthesis and secretion of hormones
from the ____.
anterior lobe of the pituitary (adenohypophysis)
adenohypophysis
• Hypothalamic hormone TRH (thyrotropin releasing hormone) - hormone is going to activate pituitary to release the first hormone ____
○ TRH travels to anterior pituitary and gland responds by releasing TSH
○ TSH hormone will act on thyroid gland (endocrine target organ) which will produce
second hormone
○ Second hormone in this case is ____ we saw this morning
• CRH stimulates release of ACTH by pituitary, hormone acts at level of ____ glands to induce secretion of glucocorticoids
• Main regulatory mechanism is ____ feedback!
○ Hormone 2 acts through negative feedback mechanism to inhibit adenohypophysis to drop secretion of hormone 1 and inhibit hypothalamus to inhibit secretion of releasing hormone
• Example: if hormone 2 is Thyroxine and T3, thyroid hormones will act in negative feedback mechanism to inhibit adenohypophysis so drop in synthesis of ____ that will have another negative feedback mechanism to prevent release of TRH
TSH
T3 and T4
suprarenal
negative
TSH
• Prolactin: secreted in response to secretion of hypothalamus known as ____ (prolactin releasing
factor) but remember this is a hormone!
○ Prolactin releasing hormone (PHF) acts on ____ to release prolactin
○ Prolactin is 1st hormone but WILL NOT act directly on gland
○ Prolactin stimulates growth and development of ____ during pregnancy
○ In this particular case, regulatory mechanisms shown here on left side of slide, prolactin acts through negative feedback mechanism to inhibit secretion of ____ by
hypothalamus therefore downregulating its own secretion
○ It can also act in a positive feedback mechanism to stimulate synthesis of
hypothalamic inhibitor factor known as ____ or prolactin-inhibiting hormone
• Now we know PIH is actually ____; PIH and dopamine = same molecule!
• What this means is that high levels of prolactin will increase secretion of PIH in hypothalamus that will also inhibit secretion of ____ = double feedback
mechanism
PRH
ant pit
mammary glands
PRF
PIH
dopamine
prolactin
• Another example is shown by secretion of growth hormone
○ Hypothalamus releases releasing factor and inhibiting factor
• Inhibitor factor - GH-IH also known as ____
• More commonly referred to as somatostatin
• Releasing factor - GH-RH
○ Same kind of system
• RH released by hypothalamus is released and stimulates synthesis of ____ that can act on some tissues but most importantly in liver, receptors for GH that induce synthesis of different family of hormones known as somatomedins
• Somatomedins are known as insulin like GF specifically ____ or ____
• Also have dual circuitry
• Actual effect of GH in many tissues (not all) is mediated by ____, not
growth hormones itself
• Effect of GH on muscle and bone is actually mediated by ____ but not by growth
hormone directly
• Circulatory similar to prolactin - negative feedback of releasing hormone and
positive feedback activation or stimulation of inhibiting hormone resulting in lower levels of GH in response to higher levels of somatomedins
somatostatin GH IGF-1 somatomedin-C1 GH IGF
Posterior Pituitary Gland (Neurohypophysis)
ADH
Stimulates ____ resorption by the renal tubules.
Oxytocin
Stimulates ____ of the uterus during birth and secretion of ____ from breasts during nursing.
water
contractions
milk
Anterior pituitary gland (adenohypophysis)
GH
Controls ____ and growth.
Prolactin
Controls ____ development and milk production.
Thyrotropin (TSH)
Stimulates growth of thyroid and production of ____.
Adrenocorticotropin (ACTH)
Stimulates growth of adrenal ____ and production of ____ hormones (glucocorticoids, androgens and mineralocorticoids).
Lutenizing hormone (LH) Controls production and release of \_\_\_\_ and progesterone by ovary and of \_\_\_\_ by testis.
Follicle-stimulate hormone (FSH)
Stimulates growth of ____ in ovary and of ____ in testes
metabolism breast thyroxine cortex cortical estrogens testosterone graafian follicles seminiferous tubules
Pituitary Gland Hormones: Growth Hormone
• Regulation and control of secretion of growth hormone (GH):
○ Start at level of ____ where there is GH releasing hormone released by hypothalamus and will act at level of anterior pituitary specifically at ____ cells that will produce growth hormone that circulates at blood stream and one example where it will act is at liver where there are specific hormones for GH
○ GH stimulates liver to synthesize second hormone like ____ and IGF-1
○ Same regulatory feedback circuits and inhibitory factor at level of hypothalamus
(____) which is inhibiting factor
○ What IGF regulates:
• Growth of ____ bones in length by acting at level of ____ plates (will become epiphyseal plates
hypothalamus acidophil somatomedin somatostatin long epiphyseal
Pituitary gland hormones: GH
Remember from last year, cells responsible for growth of bone are osteoblasts and they have receptors for IGF-1 for somatomedin-C so response to increased levels of IGF-1, osteoblast will react by producing components of matrix of the bone including:
• ____
• Many other proteins
• Facilitating deposition of ____ mineral
• Increased levels of IGF will produce increase levels in ____ during period of bone growth
collagen
hydroxyapatite
bone
Pituitary gland hormones: prolactin
Also wants to highlight prolactin:
• Prolactin is synthesized and secreted by anterior pituitary by same acidophil cells in response to ____ (prolactin releasing factor) and in minor way responds to ____ (thyrotropin releasing
hormone) but more important is PRF
• Prolactin has direct effect on ____ tissue only after giving ____ when process of lactation is about to begin
○ Prolactin produces resting mammary gland into active form meaning increase in ____ of mammary glands, cell differentiation and then secretion of components in milk
PRH TSH mammary gland birth complexity
Pineal gland
- Lies in ____ portion of roof of third ventricle.
- Contains ____.
- Synthesizes ____:
- Derives from ____.
- Sets ____ rhythms.
posterior pinealocytes melatonin tryptophan circadian
IMPORTANT POINTS (summarized): • What melatonin is derived from \_\_\_\_ • Produced in \_\_\_\_ • Melatonin helps to reset internal \_\_\_\_ ○ In absence of melatonin, internal clock of organs (all cells have internal clock) all of those clocks will begin to drift however by rhythm of inhibition of secretion of melatonin - those clocks are reset every \_\_\_\_ hours so entire body works in more coordinated way
tryptophan
dark
clock
24
Thyroid Gland
- Located along the ____ of the neck.
- Thyroid hormones regulate metabolism:
- ____ Effect: Increased energy consumption → increased heat generation.
- Amino acid-derived hormones: • ____ (T3).
- ____ (T4).
- Peptide hormone:
- ____ metabolism.
midline calorigenic triiodothyronine thyroxine calcitonin:calcium
Thyroid hormones
• After iodination and protonation of thyroglobulin (last slide) we have thyroid hormone that reaches cell
• Thyroid hormones can cross plasma membrane and two places of action”
○ ____
○ ____
○ Receptors for thyroid hormones at level of mitochondria
○ Activation of receptors and binding hormone to mitochondrial receptors increases ____
production - increases rate ____ takes place
• ATP production or activation of oxidative phosphorylation chain with all ____ reactions
produces heat so these binding of thyroid hormones to mitochondria and activation of mito metabolism increases generation of ____!
○ Part of calorigenic effect
• Another mechanism that thyroid hormones function on target cells is by binding receptor forming complex that acts as ____
○ Specific genes responsive for transcription factor so certain genes will be induced and transcribed in response to binding of thyroid hormone
• Nuclear function together with ____ function comprises full target cell response
• Some of the genes that will be increased in transcription and translation in thyroid hormones
are involved in mitochondrial metabolism
○ End effect is increase in heat generation in maintenance of internal body temperature
nucleus
mitochondria
ATP
ox phos
refox
heat
TF
mitochondrial
Thyroid gland: thyroid hormones
In terms of regulation of these mechanisms carried out by thyroid hormone, we can imagine disruption in homeostasis of body
• In normal conditions:
○ Body at normal temperature
○ Normal thyroid hormone concentrations
• Imagine for some reason our body temperature ____ (i.e. trying to catch a train at 4F as Segade was) aka homeostasis disturbed:
○ Body temperature comes down, what thyroid does is to activate neural reflex to induce hypothalamus to release ____
○ TRH acts on ____ so adenohypophysis releases ____ which acts on thyroid gland so thyroid produces ____ thyroid hormones
○ Thyroid hormones will reach target cells, they will increase production of ____
○ Normal ____ has been restored
drops TRH adenohypophysis TSH T3 and T4 heat homeostasis
Thyroid gland: calcitonin
In addition to the two better known thyroid hormones, thyroid also produces peptide hormone known as ____:
• We have thyroid follicle, most of cells produce thyroid hormones but small population of cells know as ____ cells in follicle that produce this peptide hormone
○ Since it is ____ hormone, secreted by secretion pathway
○ Calcitonin receptor is on ____ (cell responsible for modifying bone)
• Osteoclast has receptor for calcitonin so upon binding of receptor for osteoclast, will respond by becoming ____
• Osteoclasts form these cavities in bone (Howship’s ____) and show ____ border to indicate active cell
○ Upon binding of calcitonin to receptor, osteoclast loses ____ border indicating that the osteoclast is inactive
• Calcitonin is produced in physiologic conditions sensing levels of circulating calcium is too ____
• Way to drop levels of Ca2+ in blood is to stop ____ of bone
• Osteoclasts solubilizes bone mobilizing Ca2+ ions but this is one mechanism where
body tries to return high Calcium in body to normal levels
calcitonin
C
peptide osteoclast inactive lacunae ruffled ruffled high resorption
Parathyroid glands
- Embedded in ____ surface of the thyroid gland.
- Secrete peptide hormone parathyroid hormone (PTH).
- Effects of PTH: Regulation of plasma [____+].
- Osteoclast ____:
- ↑ release of Ca2+ from bone,
- Osteoblast ____:
- ↓ Ca2+ deposition in bone
- ↑ reabsorption of ____+ at the kidney, reducing loss.
- Stimulation of secretion of ____ by the kidney.
- Effects ____ or enhance PTH.
- Enhances ____+, PO43- absorption by digestive tract.
posterior
Ca2
stimulation inhibition Ca2 calcitriol complement Ca2
Osteoblast/osteoclast cross-talk: coupling
• This is osteoblast-osteoclast cross talk
• “this is one of my favorite slides of D1 - Segade”
○ Should remember that osteoclast lineage is induced to differentiate mature into active osteoclast through interactions with osteoblast
○ ____ is master regulator of osteoclast differentiation
○ Indicated by arrow is osteoblast has receptor for ____
○ What PTH does is to increase production of 2 important molecules:
• ____
• M-CSF ligand
○ Osteoclast lineage is part of monocyte macrophage lineage
• To induce differentiation of immature of monocyte into ____ (1st step of differentiation), need interaction of ____ ligand produced by osteoblast with receptor on osteoclast lineage
• This induces differentiation of osteoclast to macrophage and then to osteoclast ____
• Intimate precursor interaction with osteoblast and osteoclast
• Receptor produced known as RANK that is receptor for activation of ____
• Interaction induces final stages of osteoclas
Increased levels of PTH in response to low levels of calcium in circulation will increase circulation of ____ and expression of ____
• Therefore what osteoblast is doing is differentiating more osteoclasts, attach to bone and solubilize bone matrix thus releasing ____ ion
osteoblast
PTH
RANKL
macrophage M-CSF precursor NFkB RANKL M-CSF calcium
Parathyroid glands: PTH
Imagine calcium levels in blood ____
• Induces PT gland to secrete PTH
• Through all mechanisms before, release of Ca from bone, enhance reabsorption in ____, stimulation of calcitriol (enhanced calcium absorption of GI tract) - all mechanisms together increase levels of calcium in blood therefore homeostasis in blood
• Opposite mechanism on slide - calcium levels are too high
○ Thyroid gland C cells produce ____
• Will have decrease in calcium levels and homeostasis is restored again
drop
kidneys
calcitonin
