Functions of Pituitary Hormones Flashcards
What are the functions of the hypothalamus in terms of regulating pituitary functions? (3)
- Regulates the function of thyroid, adrenal, and reproductive glands.
- Directly responsible for somatic growth, lactation, milk secretion and ejection
- Maintains body fluid homeostasis
What is pulsatile production of hormones and what are examples of such hormones? (4)
Burst-like production or episodic
Examples:
1. Thyrotropin
2. TRH
3. Gonadotropin-releasing hormone
4. Growth hormone
Where are the hormones of the posterior lobe synthesized?
In the upper part of the neurosecretory cell
Where are the hormones of the posterior lobe released? From where?
Into the general circulation from the endings of supraoptic and paraventricular neurons which are in the posterior lobe
What are the hormones of the posterior lobe of the pituitary gland?
Oxytocin and ADH
Where are the hormones of the anterior lobe formed?
In the anterior lobe in the endocrine cells
Where are the anterior lobe hormones secreted? From where?
Into the portal hypophysial circulation, from the endings of arcuate, preoptic, and other hypothalamic neurons
What is the function of the anterior lobe hormones?
They regulate (activate or inhibit) teh endocrine cells to produce the different pituitary hormones of the anterior lobe
What are the hormones of the anterior lobe (examples)? (6)
- TSH
- ACTH
- FSH & LH
- GH
- PRL
- Endorphins
What is the target of endorphins?
The pain receptors in the brain
Where are the cell bodies of the nerves that secrete posterior lobe hormones located?
Supraoptic and paraventricular nuclei of the hypothalamus and NOT in the posterior pituitary gland itself
What are ADH and Oxytocin?
Polypeptides each containing nine amino acids, two genes located on the same chromosome region, at a very short distance from each other
What does the AVP gene code for?
AVP (ADH) and neurophysin II
What does the OXT gene code for?
Oxytocin and neurophysin I
What is the role of neurophysin?
Tranposrt or carrier protein for AVP and oxytocin, from the nuclei down to the posterior lobe cell ends where they are stored
What is the Pre-Pro-Arginine Vasopressin/Neurophysin I?
The precursor molecule for vasopressin (ADH)
What is neurophysin I?
A carrier protein that stabilizes vasopressin during tramsport within secretory vesicles
What is the function of vasopressin-associated glycopeptide?
Helps in proper hormone folding and storage
What is the Pre-Pro-Oxytocin/Neurophysin II?
The precursor molecule for oxytocin
What is the role of oxytocin?
Involved in uterine contractions during labor and milk ejection during lactation
What is neurophysin II?
A carrier protein that binds oxytocin and facilitates its transport within vesicles
What is the processing of vasipressin like?
Pre-pro-vascopressin
Pro-vasopressin
Stoarge and release
What is pre-pro vasopressin?
Initial synthesized molecule which includes:
1. Signal peptide
2. Vasopressin
3. Neurophysin II
4. Small glycoprotein sequence
When does pre-pro-vasopressin become pro-vasopressin?
After the removal of the signal peptide, processing occurs in the Golgi apparatus
What is the process of removal of the signal peptide to form the pro-vasopressin?
Cleavage of lys-arg bonds releases:
1. Vasopressin
2. Neurophysin II
3. A glycopeptide
What is the effect of ADH on the nephrons of the kidneys?
Increases permeability of distal collecting tubules to H2O
What is the effect of ADH on the arterioles through-out the body? (3)
- Causes vasoconstriction through the V1 receptor coupled to Gaq/IP3 and Ca2+ increase
- Increase in vascular resistance with no effect on muscle membrane potential
- Increase in ADH –> increase in BP
What is the effect of oxytocin on the uterus?
Stimulates uterine contractionsn
What is the effect of oxytocin on the mammary glands?
Stimulates milk ejection during breast-feeding
Which messenger systems does ADH activate?
- IP3/Ca2+
- cAMP
What is the effect of ADH on principle cells?
- Acts on G-as, which increases cAMP, which then causes the activation of PKA: synthesis of aquaporin 2 and trafficking of aquaporin 2
- Increases water re-absorption by distal tubules and collecting ducts of the kidneys
- Decreases osmotic pressure of the blood: more concentrated urine and less concentrated plasma
How does blood volume control the release of ADH?
A decrease in blood volume (≥ 10%) stimulates the mechanoreceptors in the great arteries like the aorta and carotids) & right atrium –> Increase in ADH
How does an increase in blood osmolality affect ADH release?
An increase in osmolality or decrease in blood volume affects neurons in the hypothalamus, resulting in an increase in ADH release from the pituitary
What is the effect of increased ADH on the kidneys?
ADH increases water reabsorption in the kidney, resulting in retention of a greater volume of water in the blood and reduced urine volume –> decreased blood osmolality –> increase in blood volume
What is the ADH axis? (7)
Water deficit –> Increase in extracellular osmolarity –> Incresae in ADH secretion –> Increase in plasma ADH –> Increase in H2O permeability in distal tubules, collecting ducts –> Increase in H2O reabsorption –> Decreased H2O excreted
How does age affect the control of ADH?
Increase in ADH secretion which means more water retention & hyponatremia
What other factors increase the secretion of ADH?
Pain, emotional stress and physical trauma
Drugs
What type of drugs increase ADH secretion?
Morphine
Barbiturates
Nicotine
What are the factors that decrease ADH secretion?
Alcohol
What are the effects of hyposecretion of ADH?
- Neurogenic/central diabetes insipidus
- Nephrogenic diabetes insipidus
- Primary or secondary to drug kidney dysfunction, autoimmune
What is neurogenic or central diabetes insipidus?
Problem in the hypothalamus or post-pituitary gland, infections or tumors
What kind of mutation can cause neurogenic/central DI?
Mutation in AVP prohormone-AVP or neurophysin II
What is nephrogenic DI?
Resistance of V2 receptors in collecting ducts of the kidneys; aquaporin
What are the symptoms of DI?
Polyuria –> 20L/day
Polydyspia
Decrease in specific gravity of urine (dilated urine)
Increase in plasma osmolality
What is the syndrome of inappropriate antidiuretic hormone? (SIADH)
It is a condition in which the body makes too much ADH, rare case
What is the effect of SIADH?
Low urine output
Hyponatremia
Low serum osmolality
High urine specificity
Oedema
Mental status can change if edema is cerebral –> coma
What is oxytocin?
Produced mainly by the cell bodies in the hypothalamus, supraventricular nucleus
Cyclic peptide: 9 amino acids
Maturation of what leads to oxytocin and neurophysin?
Maturation of the prehormone (oxytocin-gly-lys-arg-neurophysin I)
What is the function of endopeptidase in the prohormone maturation of oxytocin?
Cleaves the pre-hormone to produce Oxytocin-gly + Neurophysin I
What is the function of carboxypeptidase B in the prohormone maturation of oxytocin?
Further processes the molecule by removing additional residues
What is the function of a-amidating enzyme in the prohormone maturation of oxytocin?
Modifies the peptide to produce the final active oxytocin molecule
What is the catabolism of oxytocin like?
It is broken down by enzymes like cystine aminopeptidases into inactive fragments, limiting its duration of action
How does oxytocin exert its effects?
Oxytocin exerts its effects via oxytocin receptors which are G-protein coupled receptors
What is the oxytocin signaling pathway like?
- Oxytocin binds to the receptor
- The G-protein activates Phospholipase C
- Phospholipase C cleaves PIP2 into:
–> Inositol Triphosphate (IP3)
–> Diacylglycerol (DAG) - Increased intracellular Ca2+ and protein kinase C activity –> muscle contraction
What is the function of IP3?
Triggers release of Ca2+ from the sarcoplasmic reticulum
What is the function of DAG?
Activates protein kinase C
What are the targets of oxytocin?
Contraction of mammary gland
Contraction of smooth muscles of the uterus –> enhance labor
How does oxytocin work on the mammary gland?
An OT receptor-signaling dependent involving prostaglandin formation and myosin phosphorylation, leading to breast myoepithelial cell contraction & ejection of milk
What is the action of oxytocin on the uterus? (4)
- Oxytocin binds to its receptor on uterine muscle cells,
- Activates a G-protein signaling cascade –> calcium release,
- Activation of myosin light chain kinase (MLC kinase), and myosin phosphorylation, –> muscle contraction.
- Prostaglandin production and RhoA/ROK activation further enhance contractility. –> Stimulation of strong uterine contractions to facilitate labor.
What are the controls of oxytocin secretion during lactation?
- Stimulation of nipply (sucking reflex) –> Increases oxytocin
- Visual or auditory stimuli from the baby –> Increases oxytocin release
What are the controls of oxytocin release?
- Distention of uterus & stretching of the cervix during delivery –> Increase in oxytocin release (afferent nerves) –> Uterus contraction
- Alcohol –> Decrease in oxytocin secretion
- Progesterone –> Decrease in uterine sensitivity to oxytocin
- Estrogen –> Increase in uterine sensitivity to oxytocin
- Psychological and emotional factors –> Decrease in oxytocin
Which psychological and emotional factors decrease oxytocin?
Fear, anxiety and pain
What are the effects of oxytocin on Adipose Tissue (Fat Cells)?
- Increases lipolysis and beta-oxidation of fatty acids
- In small adipocytes, there is a decrease in leptin and an increase in adiponectin
What are the effects of oxytocin on Insulin Sensitivity and Glucose Metabolism?
- Enhances insulin sensitivity in tissues like muscle and liver, improving glucose uptake,
- Stimulates glucose uptake in muscle cells through pathways involving PI3K, Ca-CAMKK, and AMPK, which are important for cellular energy regulation
What are the effects of oxytocin on the Pancreas?
- Increases insulin release from pancreatic beta cells via pathways such as protein kinase-C (PKC)
- Promotes β-cell regeneration in the pancreas, potentially improving pancreatic function and insulin production
What are the hormones secreted that are secreted by pituitary cells? (6)
- TSH
- ACTH
- FSH
- LH
- hGH
- PRL
What is the anatomical relationship of the hypothalamus and the anterior pituitary gland?
The anterior pituitary gland is connected to the hypothalamus by a portal system: “hypothalamic-hypophysial portal vessels”
What is the physiological linkage between the hypothalamus and the anterior pituitary gland?
The hypothalamus secretes hormones called “hypothalamic releasing & inhibitory hormones” that regulate anterior pituitary secretions
What are the hypothalamic neurons?
The hypothalamus contains specialized neurosecretory cells in nuclei like the arcuate, preoptic, and paraventricular nuclei. They secrete the hormones
What is the portal hypophyseal circulation?
A specialized blood vessel network connecting the hypothalamus to the anterior pituitary
What are the effects of the hypothalamic hormones on the anterior pituitary?
Releasing hormones: stimulate secretion (e.g., GnRH → LH/FSH secretion).
Inhibiting hormones: suppress secretion (e.g., somatostatin → inhibits GH, dopamine → inhibits prolactin).
What are the targets of each pituitary hormone?
- TSH → thyroid gland
- ACTH → adrenal cortex
- LH/FSH → gonads
- GH → liver and tissues
- Prolactin → mammary glands
Where are anterior pituitary hormones transferred to?
They have transferred down the parvicellular axons at the median eminence –> released in a merocrine fashion into the circulation –> hormones reach the portal vein where they target specific cell types –> binding of the hormone to cell type, anterior pituitary hormones produced and released in an endocrine fashion
What is the effect of TRH on the anterior pituitary?
Stimulates TSH & Prolactin
What is the effect of CRH on the anterior pituitary?
Stimulates ACTH
What is the effect of GHRH on the anterior pituitary?
Stimulates GH
What is the effect of GHRIH on the anterior pituitary?
Inhibition of GH and TSH
What is the effect of GnRH on the anterior pituitary?
Stimulate gonadotropic hormones (LH, FSH)
What is the effect of PRH on the anterior pituitary?
Stimulates Prolactin
What is the effect of PRIH (dopamine) on the anterior pituitary?
Inhibits prolactin
What are the characteristics of hypothalamic-releasing hormones? (5)
- Secretion in pulses
- Action on specific plasma membrane receptors
- Transduction of signals through 2nd messenger
- Stimulation and release of stored target anterior pituitary hormones via exocytosis
- Stimulation of hyperplasia and hypertrophy of target cells
What is the role of TSH?
Stimulate the thyroid gland to produce and release thyroid hormones that regulate growth and energy balance
What is the role of FSH and LH?
Stimulate gonadal production of sex steroids, which mediate reproductive function and behavior
what is the role of ACTH?
STimulate the adrenal glands to produce steroids, which regulate hydromineral balance, inflammation and metabolism
What is the role of PRL?
Stimulate breast development and milk production
Stimulates breast development along with estrogen during pregnancy
Inhibits ovulation
What is the role of GH?
Exerts direct effects on tissue growth and indirect effects through the production of insulin-like growth factor-1, which mediates some of the growth effects of GH
What is the prolactin hormone responsible for?
Lactogenesis & galactopoiesis
How does the prolactin hormone stimulate milk production?
By the formation of casein and lactalbumin
How does the prolactin hormone inhibit ovulation?
Decreasing secretion of LH & FSH
What are the factors stimulating prolactin?
- Pregnancy
- Estrogen
- Nursing-breast
- Sleep
- Stress
- TRH
- Dopaminergic antagonists
- Serotonin
- Adrenergic antagonists
- Oxytocin
What is the origin of oxytocin?
Posterior pituitary gland
What is the origin of prolactin?
Anterior pituitary
What are the target tissues of oxytocin?
Uterus and breast muscle
What are the target tissues of prolactin?
Mammary glands of the breast
What is the effect of oxytocin?
Causes muscle contraction to expel the baby and expel milk in the breast
What is the effect of prolactin?
STimulate the milk production
What are the factors inhibiting prolactin?
Dopamine
Dopaminergic agonists
Somatostatin
Prolactin
GABA
What is GH?
Also called somatotropin, stimulates somatic growth and development, maintains normal lean body mass and bone mass in adults
Where does GH originate from?
Anterior pituitary somatotroph cells that make up 40 to 50% of the adult gland
What is the somatotropin releasing inhibitory factor?
A cyclic peptide with strong regulatory effects throughout the body
Where is somatostatin produced?
GIT, Pancreas, Hypothalamus, CNS
What are the two isoforms of somatostatin?
Short isoform works primarily on the brain
Long isoform operates in the GIT: SST14 and SST28
What is the half-life of somatostatin?
1 to 3 minutes
Where does GHRH bind to and what is its effect?
GHRH binds GPCRs linked to an increase in cAMP and PKA, essential in GH and GH receptors
–> The increase in cAMP activates the entry of Ca2+ essential for secretion
What hormone increases Ca2+ (GH cycle)?
Ghrelin –> hunger hormone, produced in the hypothalamus and the stomach
Which factors stimulate the release and synthesis of GHRH?
Stress, sleep, and exercise
Which factor inhibits the release of GH?
Somatostatin
What is the long-loop feedback of GH synthesis?
IGF-1 from peripheral tissues, especially the liver, provides negative feedback to both:
The anterior pituitary suppresses further GH release.
The hypothalamus inhibits GHRH secretion and enhances somatostatin release.
What is the JAK2-STAT pathway (GH synthesis)?
JAK2 phosphorylation: Leads to downstream signaling.
STAT5 activation: Translocates into the nucleus and promotes transcription of genes related to growth and metabolism.
When is GH secreted?
During sleep period in pulsatile production
