Hypothalamus and Pituitary Flashcards
the nuclei
that are bundles of __ in the hypothalamus that secrete hormones into ____
the nuclei
that are bundles of neurons in the hypothalamus that secrete hormones into pituitaries
Hypothalamus integrates many signals
e.g. ___
Hypothalamus integrates many signals
e.g. temperature, light, thirst/food,
cytokines responding to infection
Hypothalamus-Pituitary Axis work together = Neuroendocrine Paradigm
Pituitary =____
Pituitary = Hypophysis
Hypothalamus-Pituitary Axis work together = Neuroendocrine Paradigm
Anterior pituitary = ___
Anterior pituitary = Adenohypophysis
Hypothalamus-Pituitary Axis work together = Neuroendocrine Paradigm
Posterior pituitary = ___
Posterior pituitary = Neurohypophysis
Specialized regions around Hypothalamus lack \_\_\_\_ so brain can interact directly with hormones in the blood e.g. GH (growth hormone) \_\_\_ feedback
Specialized regions around Hypothalamus lack bloodbrain barrier so brain can interact directly with hormones in the blood e.g. GH (growth hormone) negative feedback
Secretion of Hypothalamic Hormones
Anterior Pituitary:
Anterior Pituitary: Hypothalamic hormones secreted by neurons through portal hypophysial vessel; then specific cell types of the anterior pituitary release hormones into the blood or get inhibited; balance of activation and deactivation both hypothalamic and pituitary hormones are released in pulses (pulsatile)
Secretion of Hypothalamic Hormones
Intermediate Pituitary:
Intermediate Pituitary
Mostly cells called melanotrophs
that produce melanocytestimulating hormone (MSH); thin
layer in between AL and PL
Secretion of Hypothalamic Hormones
Posterior Pituitary:
Posterior Pituitary: Neurons originate in Hypothalamus and project into posterior pituitary; neurons deliver hormones; then released from post pit into blood
Hypothalamus Connects nervous system to endocrine system: ____
Connects nervous system to endocrine system: stimulates many
endocrine glands – thyroid, adrenals, gonads etc. mostly through pituitary
Hypothalamus
Controls___
Controls: Temperature, appetite, thirst, fatigue, behavior, defense reactions,
circadian cycle, blood pressure
Hypothalamus Inputs (external and internal):
light smell autonomic (neural) inputs hormones (steroids & thyroid H, blood borne peptides) blood borne inputs stress immune stimuli…
Hypothalamic Outputs: (1)
1) direct innervation to adrenal medulla, kidney, parathyroid gland, pancreatic islets (fast)
Hypothalamic Outputs: (2)
2) neurosecretion = hormones secreted by hypothalamic nuclei;
hypothalamic hormones are mostly small peptides and act via
GPCR surface receptors; the hormones act on anterior or posterior
pituitary causing the pituitary to release hormones in turn (may be
fast or slower acting depending on pathway activated)
Hypothalamic Outputs:
Timing and Type of Hormone Response Highly Variable:
Some things must be fast (e.g. fight or flight, adrenaline, cortisol)
but some things must be slow (e.g. brain development via thyroid
hormone (TH) or bone growth via growth hormone (GH) and
insulin-like growth factor 1 (IGF-1 )
Hypophysiotropic H
Hypophysiotropic H – regulate release of anterior pituitary hormones; pulsatile
main function
Thyrotropin-releasing hormone (TRH)
regulation of thyroid stimulating hormone
TSH
Main function
Gonadotropin-releasing hormone
(GnRH)
regulation pituitary gonadotropins LH and
FSH (luteinizing hormone and follicular
stimulating hormone)
Main function
Somatostatin
inhibition of growth hormone (GH), TSH,
insulin, glucagon, and others
Main function
Growth hormone-releasing hormone
(GHRH)
stimulation of GH (GHRH tropic effect on
GH)
Also GHRH is trophic for somatotrophs
(helps them grow/thrive)
Main function
Prolactin-inhibiting hormone
(PIH, exactly the same as dopamine)
inhibits prolactin (PRL)
Main function
Corticotropin-releasing hormone
(CRH)
regulation of adrenocortical function,
adrenocorticotropic hormone (ACTH)
release, regulate appetite, sympathetic
nervous system and adrenal medulla
Cells of the Anterior Pituitary
Different cell types of anterior pituitary secrete different hormones controlled by
the ___ hypothalamic hormones for each___
Different cell types of anterior pituitary secrete different hormones controlled by
the upstream hypothalamic hormones for each axis
Cells of the Anterior Pituitary
Somatotrophs
Somatotrophs = GH growth hormone
Cells of the Anterior Pituitary
Lactotrophs
Lactotrophs = PRL prolactin
Cells of the Anterior Pituitary
Thyrotrophs
Thyrotrophs = TSH thyroid-stimulating hormone
Cells of the Anterior Pituitary
Corticotrophs
Corticotrophs = ACTH adrenocorticotropic hormone
Cells of the Anterior Pituitary
Gonadotrophs
Gonadotrophs = LH luteinizing hormone and FSH follicular stimulating hormone
GnRH Receptor:
: GPCR Gαq – stim. PLC receptors found in pituitary, brain,
placenta, ovary, testis
- it uses a GPCR; receptors found in
reproductive tissues, but main effect is in pituitary release of LH and FSH
GnRH Main functions (3)
Main Functions:
1. Stimulate release and synthesis of pituitary hormones, LH (luteinizing
hormone) & FSH (follicle stimulating hormone) from gonadotroph cells
2. Some axons branch to other parts of brain, limbic system (emotions)
neuromodulator
3. Placenta and ovaries make GnRH – acts locally (receptors found there);
Gonadotrophs
• Release Luteinizing Hormone (LH) and Follicular Stimulating Homone (FSH) (4)
- Both glycoproteins (structurally related)
– The effects of FSH and LH are sex specific
– In general, they bind to receptors in the ovary and testis and regulate gonadal function by
promoting sex steroid production and gametogenesis.
– Stimulated by GnRH (Gonadotropin-Releasing Hormone)
The Hypothalamic-Pituitary-Gonadal Axis (HPG)
The hypothalamus must integrate many signals and produce an appropriate response including stimulating or inhibiting endocrine glands Note that hormones downregulate themselves using negative feedback loops Note that GnRH must be pulsatile otherwise LH and FSH become desensitized
CRH
Corticotropin-Releasing Hormone
ACTH
Adrenocorticotropic Hormone (ACTH)
CRH main function
Main Function: CRH is secreted in response to stress. Stimulates
secretion of products derived from proopiomelanocortin (POMC) like
adrenocorticotropic hormone (ACTH) from corticotroph cells of ant pit
Vasopressin (VP) and angiotensin act synergistically with \_\_\_\_ to mediate \_\_\_\_ release (so VP positive regulator of \_\_\_\_\_)
Vasopressin (VP) and angiotensin act synergistically with CRH to mediate ACTH release (so VP positive regulator of ACTH)
Oxytocin (OT) inhibits the ___ mediated release of ___ (so OT negative
regulator of ____)
Oxytocin (OT) inhibits the CRH mediated release of ACTH (so OT negative
regulator of ACTH)
CRH is also secreted from the ____
CRH is also secreted from the placenta
Corticotrophs
- Release derivatives of pro-opiomelanocortin (POMC)
POMC: a polypeptide of 134 AA
–its tissue specific processing, and its
biologically active peptides ACTH and MSH
– Stimulated by Corticotropin-Releasing Hormone (CRH)
Regulation of ACTH (and Cortisol): The Hypothalamus - Pituitary - Adrenal (HPA) Axis
Cortisol helps the body respond to stress (restore homeostasis) by maintaining \_\_\_ and cardiovascular function, reduce\_\_\_ responses, maintain blood \_\_\_\_ levels and regulate the metabolism of \_\_\_, \_\_\_\_, and \_\_\_ ; regulated mainly by circadian rhythm (\_\_\_release), stress, feedback inhibition by \_\_\_\_ and \_\_\_
Cortisol helps the body respond to stress (restore homeostasis) by maintaining blood pressure and cardiovascular function, reduce immune responses, maintain blood glucose levels and regulate the metabolism of proteins, carbohydrates, and fats; regulated mainly by circadian rhythm (ACTH release), stress, feedback inhibition by cortisol and ACTH
Negative feedback Short - Long - - fast (nonnuclear) - slow (nuclear)
Negative feedback Short - ACTH inhib own secretion Long - Cortisol can act on the pituitary or hypothalamus to decrease ACTH synthesis and can be: - fast (nonnuclear) and depends on the rate of change of cortisol levels - slow (nuclear) and depends on the absolute levels cortisol and involves transcription
A negative feedback loop of ____ on the
secretion of ___ also exists.
A negative feedback loop of ACTH on the
secretion of corticotropin-releasing
hormone (CRH) also exists.
ACTH followed by a cortisol ___ before
waking and ___ as the day progresses;
stress may stimulate ____ (mediated by __ and ___); low while sleeping
ACTH followed by a cortisol peak before
waking and declines as the day progresses;
stress may stimulate ACTH (mediated by VP
(vasopressin; cover next in posterior pituitary)
and CRH); low while sleeping
Lactotrophs Release Prolactin (PRL)
-A 198 aa protein
–During pregnancy it helps in the preparation of the mammary glands for
future milk production.
–Following birth, stimulates the production of milk products (protein and
lactose synthesis, water excretion and sodium retention)
–Dopamine aka PIH (prolactin inhibiting hormone) inhibits PRL, so main
regulatory hypothalamic hormone is inhibitory
–Stimulated by sleep and stress, but mainly suckling stimulation by baby
nursing at breast
–Important in men and women for sexual gratification
–In women who aren’t pregnant, prolactin helps regulate the menstrual
cycle
–In men, prolactin affects sperm production
Dopamine (aka Prolactin Inhibitory Hormone) Regulates Milk Production via Inhibiting PRL
Dopamine Receptors:
Gαi - inhibits AC, ↓ cAMP levels
Dopamine (aka Prolactin Inhibitory Hormone) Regulates Milk Production via Inhibiting PRL
Main Function
Role is inhibitor of prolactin by binding receptor on
lactotrophs, so disruption or inhibition of dopamine leads to an increase
in prolactin (for milk)
Dopamine is an amino acid derivative
Prolactin Axis
PRL stimulates breast development and milk production; inhibits ___
synthesis thus inhibiting ___ in females and ___ in males
(decreases ___ as a response), and increases ___ secretion
(negative feedback)
PRL stimulates breast development and milk production; inhibits GnRH
synthesis thus inhibiting ovulation in females and spermatogenesis in males
(decreases FSH/LH as a response), and increases dopamine secretion
(negative feedback)
___ regulation by breast feeding infant
stimulates nipple ___ that
tell hypothalamus to increase ___
Positive regulation by breast feeding infant
stimulates nipple mechanoreceptor that
tell hypothalamus to increase PRL
TRH Receptor:
main function
TRH Receptor: GPCR
Main Function: Stimulates release of thyroid stimulating hormone (TSH)
from thyrotroph cells of anterior pituitary
Thyrotrophs
Release Thyroid Stimulating Hormone (TSH) (4)
-glycoprotein
– Stimulates all aspects of thyroid gland function - including thyroid
hormone synthesis and release. TSH also causes an increase in
thyroid gland size and vascularization.
– Stimulated by thyrotropin-releasing hormone (TRH); inhibited by
somatostatin both from the hypothalamus
– also inhibited by thyroid hormone (TH, T3 and T4
) negative
feedback loop
Regulation of TH Axis
step 1
1) Neurons from hypothalamus secrete thyrotropin-releasing hormone (TRH) into portal veins that provide a direct route for TRH to the anterior lobe cells
Regulation of TH Axis
Step 2
2) Thyrotrophs in anterior pituitary are stimulated by TRH and secrete TSH (thyroid-stimulating hormone) into the pituitary venous system; inhibited by somatostatin from hypothalamus
Regulation of TH Axis
Step 3
3) Cells in thyroid are stimulated by TSH and secrete thyroid hormone (TH) into the capillaries for
transport to target tissues or via blood stream back to hypothalamus and pituitary. TH uses iodide –
critical to structure and iodide (I) acts as regulator too
Regulation of TH Axis
Step 4
4) TH transported into cells of
target tissue
Regulation of TH Axis
Step 5a
5a) Negative Feedback: serum T3 and T4
levels regulate TRH and TSH
Regulation of TH Axis
Step 5b
5b) Negative Feedback:
excess iodide inhibits (iodide
required for TH; is also a
regulator)
Somatostatin Regulates the Growth, Thyroid and Insulin Axes by Inhibition
Somatostatin Receptor:
: GPCR Gαi – inhibits AC, ↓ cAMP levels,↓GH and
↓TSH secretion (binds to cell surface receptors on somatotrophs and
thyrotrophs)
Somatostatin Regulates the Growth, Thyroid and Insulin Axes by Inhibition
Main Functions
: Inhibits secretion of GH and TSH from pituitary, also made
in pancreas, gut and thyroid
Somatostatin Regulates the Growth, Thyroid and Insulin Axes by Inhibition
Two forms
Two forms: SS14 in hypothalamus and SS28 (N-term extended) in gut;
differential processing in different tissues allows different function of SS
Growth Hormone-Releasing Hormone (GHRH) Regulates Growth Axis via ____
Growth Hormone-Releasing Hormone (GHRH) Regulates Growth Axis via Growth
Hormone (GH)
GHRH Receptor:
GPCR Gαs – activates AC which then produces cAMP, ↑GH secretion
GHRH Characteristics:
Released in pulses (like the other hypothalamic hormones)
-this leads to pulsatile increases of GH in circulation when stimulates
somatotroph cells of anterior pituitary
Somatotrophs
• Release Growth Hormone (GH) (5)
A 191 AA protein; mainly non-glycosylated
– Stimulates the production of insulin-like growth factor 1 (IGF-1), a
mediator of the indirect growth promoting effects of GH
– Also exerts direct effects on lipolysis, AA uptake in various
tissues, protein synthesis in the liver, and opposes insulin actions
– Stimulated by growth hormone-releasing hormone (GHRH) from
hypothalamus; inhibited by somatostatin
– Negative feedback on somatotrophs to regulate self = autocrine
GHRH and Somatostatin are Reciprocal hormones (2)
- Growth Hormone Releasing
Hormone (GHRH) stimulates
synthesis and secretion of GH by
increasing cAMP. - Somatostatin (SS) inhibits GH
release by decreasing cAMP
Both ____ (GHRH) and ____ (SS) act on
same somatotroph cells via ____ and stimulate or inhibit
synthesis and secretion of GH by increasing or decreasing ____.
Both Growth Hormone Releasing Hormone (GHRH) and Somatostatin (SS) act on
same somatotroph cells via adenylyl cyclase enzyme (AC) and stimulate or inhibit
synthesis and secretion of GH by increasing or decreasing cAMP.
Tropic H
Tropic H – hormone that stimulates a specific target
gland to secrete a different set of hormones
Trophic H
Trophic H – affect the growth, nutrition, or function of
another endocrine gland/cell
GHRH has a ___ effect on GH causing its production
and release; but GHRH is ___ for somatotrophs by
helping them grow/thrive
GHRH has a tropic effect on GH causing its production
and release; but GHRH is trophic for somatotrophs by
helping them grow/thrive
