Hypothalamus and Pituitary Flashcards
Pituitary function is regulated by ___________ produced in the ________
Pituitary function is regulated by neurohormones produced in the hypothalamus.
What are 3 examples of hypothalamic nuclei (clusters of neurons) found in the hypothalamus?
- Supraoptic nuclei
- Paraventricular nuclei
- Preoptic nuclei
What is the function of hypothalamic nuclei?
They produce hormones that control pituitary function
The pituitary gland is also known as the…
Hypophysis
The adenohypophysis includes which 3 components?
- Pars tuberalis (tuberal lobe)
- Pars intermedia (intermediate lobe)
- Pars distalis (anterior lobe)
The neurohypophysis includes which 2 components?
- Infundibulum (neural lobe)
- Pars nervosa (neural lobe aka posterior pituitary)
The anterior pituitary is embryologically derived from…
- What origin does the anterior pituitary have?
Dorsal outgrowth of the buccal cavity (roof of the mouth)
- Epithelial origin (non-neuronal origin)
The posterior pituitary is embryologically derived from…
- What origin does the posterior pituitary have?
Embryologically derived from the brain
- Neural origin
What is the intermediate lobe?
Region in between anterior and posterior pituitary associated with adenohypophysis.
True or false: the intermediate lobe is present in all organisms.
False, the intermediate lobe is not present in some mammals, birds, hagfish and lamprey.
Describe hormone production/secretion in the posterior pituitary (neurohypophysis)
Neurosecretory neurons in hypothalamus make neurohormones. Hormones travel down axons into the posterior pituitary and stored in nerve terminals until stimulatory signal stimulates secretion of the hormones into circulation.
Describe hormone production/secretion in the anterior pituitary (adenohypophysis)
Neurosecretory neurons in hypothalamus make neurohormones. These hormones are secreted into the hypothalamic-hypophyseal portal system through the median eminence. These hormones target the secretory cells in the anterior pituitary gland. The anterior pituitary gland then secretes its own hormones.
True or false: Hypophysiotropic hormones that target the posterior pituitary can be found in circulation
True
True or false: Hypophysiotropic hormones that target the anterior pituitary can be found in circulation
False
What class of hormones are released from the hypothalamus and the pituitary?
Hypophyseal hormones
What 2 hormones are secreted by the posterior pituitary? How many amino acids do they consist of?
- Vasopressin
- Oxytocin
Each contain 9 amino acids
Oxytocin and vasopressin are both (linear/cyclic) due to…
What is this form important for?
Cyclic due to the presence of Cys
- forms disulfide bonds
- Cyclic structure is important for their stability
True or false: There are other structurally different neurohypophyseal hormones found within mammalian and non-mammalian vertebrates
True
What nuclei in the hypothalamus are vasopressin and oxytocin produced in?
Synthesized within the cell bodies of neurons located in the supraoptic and paraventricular nuclei of the hypothalamus
- The neurons either produce oxytocin or vasopressin
Arginine Vasopressin (AVP) is the form of vasopressin present in…
Humans
Arginine Vasopressin (AVP) is also known as…
Antidiuretic hormone (ADH)
Analogs of what hormone are used for control of blood pressure?
ADH
Increase in AVP secretion (increases/decreases) urination
Decreases
What do the V1 receptors of AVP mediate?
Vascular smooth muscle contraction (smooth muscle in blood vessels)
- Controls blood pressure
What do the V2 receptors of AVP mediate?
Produces the renal action of AVP
True or false: AVP only mediates blood pressure and hydration in humans
False
- AVP also acts to facilitate memory consolidation
- AVP treatment improves short-term memory in aged humans
What two parameters affect AVP secretion?
Change in blood pressure and change in ion osmolality
Describe the control of AVP secretion pathway due to a change in blood pressure (5 steps)
- Decreased blood pressure
- Activation of baroreceptors
- Increased AVP secretion
- Increased water uptake (V2) and increased constriction of the arterioles (V1)
- Increase in blood pressure
Describe the control of AVP secretion pathway due to change in blood osmolality (5 steps)
- Increased blood osmolality (increased [Na+])
- Activation of osmoreceptors in CNS
- Increased AVP secretion
- Increased water retention (V2) and increased Na+ secretion (V2)
- Increased urine concentration and decreased urine volume
True or false: The AVP response to plasma osmolality is very sensitive
True
- 1% change activates AVP release
As plasma osmolarity increases, plasma AVP…
Increases linearly
As plasma AVP increases, urine osmoality…
Increases linearly
What 8 things stimulate AVP release?
- Increase in extracellular fluid osmolality
- Decrease in plasma volume
- Decrease in blood pressure
- Increased Na+ in cerebrospinal fluid
- Pain
- Stress
- Increase in temperature
- Certain drugs
What two things inhibit AVP release?
- Decrease in temperature
- Ethanol (why you have to pee a lot when you’re drunk)
What three drugs stimulate AVP release?
- Nicotine
- Opiates
- Barbiturates
What are the two functions of oxytocin?
- Control of milk release after parturition
- Uterine contraction and parturition
How does oxytocin control milk release?
Oxytocin stimulates milk ejection by contracting the myoepithelial cells in the mammary gland
- Suckling stimulates sensory nerves in the areolae and nipples of the breast
True or false: oxytocin stimulates milk production
False
- Oxytocin stimulates milk RELEASE, not production
Explain how oxytocin controls uterine contractions (5 steps)
- Fetus enters the birth canal
- Stretch receptors in the lower segment of the uterus, the cervix and the vagina send signals to hypothalamus
- Increased secretion of oxytocin from hypothalamus/posterior pituitary
- Stronger uterine contraction
- Further descent of the fetus and further distention acts on hypothalamus through positive feedback to stimulate more oxytocin release
True or false: Both the target cells and the pituitary can acts on the hypothalamus through positive and negative feedback
True
True or false: target cells can act on both the pituitary and the hypothalamus through positive and negative feedback
True
True or false: the pituitary tends to release stimulatory and inhibitory hormones
False, usually its the hypothalamus that releases stimulatory/inhibitory hormones
What 5 cell types are present in the anterior lobe?
- Gonadotropes
- Lactotropes
- Somatotropes
- Corticotropes
- Thyrotropes
Gonadotropes in the anterior pituitary secrete…
LH and FSH
Lactotropes in the anterior pituitary secrete…
Prolactin
Somatotropes in the anterior pituitary secrete…
Growth hormone (GH)
Corticotropes in the anterior lobe secrete…
ACTH
Thyrotropes in the anterior lobe secrete…
TSH
In general, what are the three families of peptide hormones produced in the adenohypophysis?
Family I:
- Growth hormone (GH) and prolactin (PRL) produced in anterior pituitary
Family II:
- Glycoprotein hormones (have carbohydrate moieties), produced in anterior pituitary (with some exceptions)
Family III:
- Hormones derived from Pro-opiomelanocortin (POMC) produced in anterior pituitary and interior lobe
Describe family I proteins
Both GH and prolactin consist of approximately 200 amino acids (single chain protein, linear)
Describe family II proteins in terms of what is produced and where
Glycoprotein hormones: TSH and gonadotropin hormones
- TSH, FSH and LH are produced in the anterior pituirary.
- Chorionic gonadotropin is produced in the placenta during pregnancy and is LH-like (what is measured in the urine for pregnancy tests)
Describe family II proteins in terms of structure and activity
Each glycoprotein is composed of two subunits; alpha and beta (noncovalently linked)
- Separated subunits have no biological activity
- The alpha subunit is the same for all glycoprotein hormones
- The beta subunits are different and confer a special functional property for each glycoprotein
True or false: the alpha and beta subunits of glycoprotein hormones in family II of proteins can be active seperately
False, alpha and beta subunits have to be in dimeric form to have biological activity
What 4 hormones are derived from Pro-opiomelanocortin (POMC) precursors? What are their general functions?
- Adrenocorticotropin hormone (ACTH) - stimulates activity of adrenal cortex
- Melanocyte-stimulating hormone (α-MSH, β-MSH) - target the pigmentation in the skin
- β-endorphin - pain relief
- β-lipotrophic hormone - important for lipid metabolism
How does POMC become the 4 different peptides?
POMC derived peptides are cleaved specifically by a family of prohormone convertases expressed differentially in various cell types
- So the prohormone convertase that is expressed in the intermediate lobe is different for each different cell type
α-Melanocyte-Stimulating hormone (MSH) structure
13 amino acid peptide derived from the precursor POMC
α-MSH is secreted from…
Melanotropes in pars intermedia or intermediate lobe
The pars intermedia is absent in which 4 animals?
Adult humans, whales, dolphins and birds
- infant humans have an intermediate lobe but it eventually fuses with the anterior pituitary
True or false: the size of the pars intermedia is to some extent correlated with the ability of the animal to change colour
True
What are the target cells of α-MSH? What do they stimulate?
α-MSH acts on melanocytes and stimulates dispersion of melanin granules within these cells, resulting in darkening of the skin
- Not critical for humans, but vital for lizards who need to camouflage
Dopamine (a catecholamine) is a _____ of prolactin
Strong inhibitor
Cholecytokinin (CCK) is a ____ of prolactin
Weak stimulator
What is the main controlling molecule of prolactin release?
Dopamine (through inhibition)
True or false: there is a strong stimulator for prolactin
- If true, what is the stimulator?
False
True or false: prolactin did specialize early in vertebrate evolution
False
- Prolactin did not specialize early in vertebrate evolution. Instead, it is used by different species to control a wide variety of functions
What are the 3 main (general) functions of prolactin? How can these effects be described overall?
- Reproduction
- Osmoregulation
- Growth and development
Many of these effects are species-specific (function of prolactin differs based on the species)
What are the 2 main functions of prolactin in males?
- Increase and maintain LH receptors in testis (help to sustain testosterone levels)
- Males with low prolactin tend to have a low sperm count - Increase sperm motility
What are the 5 main functions of prolactin in females?
- Stimulates lactation; it stimulates the synthesis of casein (a major milk protein) and fatty acids
- Increases progesterone synthesis
- Stimulates the migration of IgA (immunoglobulin A) lymphoblasts to the mammary gland (which are then passed onto the baby; helps with immunity)
- Osmoregulatory function in the uterus (ensures that the baby in the amniotic fluid doesn’t shrink or swell)
- There’s also evidence that prolactin plays a role in fish migrating between seawater/freshwater - High prolactin level observed during lactation reduces gonadotropin production, which suppresses sexual activity
- inhibits LH response
- evolved to reduce the chances of pregnancy while a mother is nursing its young
Growth hormone (GH) is also known as…
Somatotropin
What is the main action of GH?
The stimulation of somatic growth (skeletal and soft tissues)
How does GH exert its actions?
Both directly at the target cell or indirectly through production of growth factors (e.g. IGF-I and IGF-II, which are insulin-like growth factors)
GHRH (stimulates/inhibits) GH
Stimulates
- potent stimulator
Somatostatin (stimulates/inhibits) GH
Inhibits
IGF-I (stimulates/inhibits) GH
Inhibits
- through negative feedback on anterior pituitary
Hypoglycemia (stimulates/inhibits) GH
Stimulates
High protein meal (stimulates/inhibits) GH
Stimulates
Fatty acids (stimulate/inhibit) GH
Inhibits
Hyperglycemia (stimulates/inhibits) GH
Inhibits
Describe the physiological actions of GH in detail that lead to increased SKELETAL growth (4 steps)
- indirect growth-promoting actions
- Hypothalamus produces GHRH which targets anterior pituitary to release GH
- GH targets liver and other organs
- Liver and other organs produce somatomedins (IGF) and IGF-I binding proteins
- IF THYROID HORMONES ARE PRESENT, there is increased chondrogenesis which leads to skeletal growth
Describe the physiological actions of GH in detail that lead to increased EXTRASKELETAL growth (4 steps)
- indirect growth-promoting actions
- Hypothalamus produces GHRH which targets anterior pituitary to release GH
- GH targets liver and other organs
- Liver and other organs produce somatomedins (IGF) and IGF-I binding proteins
- IF THYROID HORMONES ARE PRESENT, there is increased tissue growth, cellular differentiation and augmentation of trophic hormone actions (growth factors)
- increased proliferation of cells = hyperplasia
Describe the physiological actions of GH in detail that lead to increased blood sugar and fat metabolism (2 steps)
- Hypothalamus produces GHRH which targets anterior pituitary to release GH
- IF CORTISOL IS PRESENT, there is increased lipolysis and and an increase in blood sugar by decreasing glucose oxidation and suppressing muscle uptake of glucose (keeps fuel in the bloodstream available for vital functions, like growing new tissues)
Humans usually have __ growth spurts
- What are they called?
2
- Postnatal growth spurt and pubertal growth spurt
Babies grow fast due to the postnatal growth spurt. Teenagers going through puberty also grow fast. What happens to their weight?
They lose weird because of increased lipolysis
In most developed countries, average height has decreased. Why?
They have high blood sugar to begin with, which decreases growth hormone production
Why does linear growth decrease after puberty (why does growth plateau)?
During puberty, increased levels of sex hormones causes fusion of epiphysis (growth plate)
- Progenitor cells that produce chondrocytes disappear.
What does GH deficiency lead to? What are the symptoms? What is the treatment?
Dwarfism if it occurs before puberty
Symptoms in adults: weakness, fine wrinkling and pale skin, loss of sex drive, genital atrophy, menstrual cycle cessation
Treatment: GH replacement before puberty. Can’t reverse after puberty due to fusion of epiphysis.
What does GH receptor deficiency lead to? What is the treatment?
A rare condition causing Dwarfism
- Irreversible (can’t correct by giving them more GH) BUT some attempts have been done to correct this using gene therapy
What does excess GH lead to before puberty? What are the symptoms? What is the treatment?
- Gigantism if GH excess occurs before puberty: disproportionately long arms and legs
- Treatment: tumour removal (that secretes GH) or somatostatin analogs
What does excess GH lead to after puberty? What are the symptoms? What is the treatment?
Acromegaly if GH excess after body growth stops: enlargement of skull, facial bones, jaw, hands, feet, soft tissues & organs which can lead to diabetes, hypertension, muscle weakness, arthritis, gonadal dysfunction and cardiovascular disease.
- Treatment: Tumour removal or somatostatin analogs
True or false: the presence of thyroid hormones are essential for normal growth function
True
- There is a synergism between thyroid hormones and growth hormone
What does low thyroid level in children or young animals lead to?
Abnormal growth and development
True or false: the shape of the thyroid is the same in all species
False
- The shape of the thyroid is different in all species
Describe the structure of thyroid follicles
Filled with a fluid called “colloid”, which is surrounded by follicular cells
- Follicular cells surrounded by blood vessels that take away the secreted hormones
Thyroid Stimulating Hormone (TSH) structure
A glycoprotein consisting of two subunits, α and β.
Thyroid hormones T3 and T4 (stimulates/inhibits) TSH
Inhibits
- negative feedback
TRH (stimulates/inhibits) TSH release
Stimulates
What three molecules does TSH stimulate specifically?
Thyroglobulin (Tg) synthesis, T3 (triiodothyronine) and T4 (tetraiodothyronine) synthesis
Chronic increase in TSH leads to… (2 things)
Overall, what does this lead to?
- Hypertrophy (increased cell size) of thyroid follicles
- Hyperplasia (increased number of cells) of thyroid follicles
Causes a tumour-like structure in the thyroid
What causes an endemic goiter?
Iodine deficiency leads to decreased synthesis of T3 and T4, which increases TSH and leads to enlargement (hyperplasia) of the gland
Thyroid hormones are derived from…
Tyrosine
Where does Tyrosine come from in thyroid hormone synthesis?
Comes from Thyroglobulin
Which thyroid hormone is the principle secretory product under normal conditions?
T4
Which thyroid hormone is the main thyroid ligand that binds thyroid hormones?
T3
What are the 4 steps involved in the synthesis of thyroid hormones?
- Iodide trapping by active transport mechanism (iodide pump)
- Oxidation of iodide (I-) to iodine (I2) mediated by iodide peroxidase and H2O2 (peroxidase is an enzyme in the pentose-phosphate pathway)
- Iodination of tyrosyl residues of thyroglobulin molecules (~600,000) to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)
- Oxidative coupling of iodinated tyrosine to form mostly T4 and a smaller amount of T3. T3 is stored in the colloid space.
Oxidative coupling of 2 DITs forms…
T4
Oxidative coupling of DIT-MIT forms…
T3
How is most of T3 produced?
Produced from the deiodination of T4 mediated by deiodinases in the tissues outside the thyroid gland, including liver, kidneys and brown fat.
What are the two main functions of thyroid hormones?
- Metamorphosis
- Growth effects
Describe how metamorphosis in amphibian larvae is mediated by thyroid hormones
- thyroid hormones stimulate metamorphosis in amphibian larvae
- Thyroidectomized tadpoles remain as tadpoles
- Treatment with thyroid hormone reverses this effect
What effect does a thyroidectomy have in birds and mammals?
Growth retardation
What effect does a thyroidectomy have in new born rats? What is the treatment for this?
Results in bone malformation of skull and delayed ossification (cartilagenous hardening into bone) of long bones
Treatment: thyroid hormone therapy beginning before 15 days of age corrects these abnormalities. After this age, hormone treatment is relatively ineffective
True or false: thyroid hormones don’t influence the eruption of permanent teeth in children
False
- In hypothyroid children, the eruption of permanent teeth is greatly delayed
True or false: Thyroidectomies in young rates or treatment with anti-thyroid drugs results in a larger than normal brain
False
- Thyroid hormone also influences the development of the nervous system
- Thyroidectomy in young rats or treatment with anti-thyroid drugs results in smaller than normal brain, reduction of the number of axons in the cerebral cortex
What can happen in terms of neural development if congenital hypothyroidism is not treated? What is the treatment?
Mental retardation
Treatment: thyroid replacement
- If begun prior to 6 weeks, potential for normal IQ
- If delayed to 6 months, average IQ is 55
Describe the metabolic functions of thyroid hormone
- Thyroid hormones maintain basal metabolic rate
- In birds and mammals, thyroid hormone increases oxygen consumption and heat production (calorigenesis)
Describe the pathway for the metabolic function of thyroid hormone in mammals, starting from prolonged cold (6 steps)
- Prolonged cold (stimulus)
- Neuroendocrine reflex stimulates hypothalamus
- Increase in hypothalamic TRH
- Increase in TSH from anterior pituitary
- Increase in T4 and T3 production
- Thermogenesis
What is the metabolic function of thyroid hormones regarding nitrogen balance?
Thyroid hormones at physiological concentrations increase protein synthesis, growth rate and results in positive nitrogen balance (more nitrogen retained in body than excreted)
What is the metabolic function of thyroid hormone regarding lipolysis?
Thyroid hormone treatment favours lipolysis and raising of free fatty acids in the blood
