Anterior pituitary function Flashcards
Hypothalamic hormones - stimulating
CRH vasopressin GnRH GRH Ghrelin PRP, PRH TRH
Hypothalamic hormones - inhibitory
Somatostatin
Prolactin inhibiting factors
CRH –> pituitary hormones
ACTH
Vasopressin –> pituitary hormones
beta lipotropin
beta endorphin
alpha MSH
GnRH –> pituitary hormones
LH
FSH
GRH –> pituitary hormones
Growth hormone
Ghrelin –> pituitary hormones
Growth hormone
Prolactin releasing prptides –> pituitary hormones
Prolactin
TRH –> pituitary hormones
TSH
Somatostatin –> pituitary hormones
INHIBITS growth hormone, thyrotropin, ACTH
Prolactin inhibiting factors –> pituitary hormones
Prolactin
Acidophil types
Mammosmmatotroph (GH, PRL)
Somatotroph (GH)
Lactotroph (PRL)
Basophil types
Corticotroph (ACTH, Endorphin, MSH, etc)
Thyrotroph (TSH)
Gonadotroph (LH, FSH)
GH effects
stimulates bone growth/protein synthesis
lipid/carb metabolism
synthesis of IGF1
Prolactin effects
lactation
testis and prostate: growth/development ???
Behaviour, immun
ACTH effects
stimulates production and secretion of GCs
stress response
homeostasis?
alpha-MSH effects
fetal growth??
skin pigmentation
inflammation
beta-endorphin effects
stress response???
TSH effects
stimulates production/secretion of thyroid hormones
thyroid growth
LH effects
ovulation
estrogen and progesternoe production
testis: development, testosterone synthesis
FSH effects
testis: development, spermatogenesis
ovary: follicle maturation, estrogen production
GH regulation
\+GHRH: stress, exercise, sleep rhythms \+GH: GHRH -GH: somatostatin GH on liver: IGF1 produced IGF1 inhibits pituitary and hypothalamus
Prolactin regulation
Breast suckling –> hypothalamus stimulated to produce TRH, PRPs?
Pituitary produces prolactin –> lactation
Prolactin stimulates hypothalamus
ACTH/CRH regulation
\+: stress CRH/AVP stimulates ACTH production ACTH on adrenal: cortisol Cortisol inhibits pituitary and hypothalamus ACTH inhibits hypothalamus
TRH/TSH regulation
TRH –> pituitary makes TSH –> thyroid makes T3/T4
T3/T4 inhibits pituitary, hypothalamus
FSH/LH regulation
Hypothalamus –> GnRH –> anterior pituitary produces LH, FSH
LH –> Interstitial cells makes testosterone –> testosterone inhibits hypothalamus and anterior pituitary
FSH acts on sertoli cells –> inhibin –> inhibits hypothalamus and anterior pituitary
MOA of releasing and release inhibiting hormones
1) at anterior pituitary cells, act via binding to specific G-protein coupled 7 transmembrane spanning receptors (GPCRs)
2) GPCRs coupled to intracellular signalling pathways
3) All have a common final step: increased Ca, exocytosis
Circadian rhythm
Diurnal
24 hour
e.g. cortisol, GH
Ultradian rhythm
pulsatile
<24 hour
e.g. GH, LH, FSH
secreted hormones are directly responsible for specific events associated with physiological cycles
help avoid receptor desensitization and associated loss in responsiveness to a hormone
Infradian rhythm
> 24 hour
e.g. menstrual cycle
Circadian rhythm control
Suprachiastmatic nucleus of the hypothalamus
Intrinsic 24 hour cycle entrained with the light-dark cycle of the environment via direct and indirect input from the retina
Modification of the intrinsic cycle arise from the retina itself, the thalamus, mid-brain, hippocampus, and pineal gland
Pituitary location
Inferior to the hypothalamus in the sella turcica (hypophysial fossa)
Covered by dura mater - sellar diaphragm
Hypothalamus nuclei
Supraoptic nuclei –> ADH
Paraventricular nuclei –> ADH, oxytocin
Superchiastmatic nucleus –> Circadian rhythm
Anterior pituitary cell types
Chromophil - acidophils (GH, PRL) basophils (ACTH, FSL, LH, TSH)
CHromophobes
Rudiments of Rathke’s pouch - colloid filled cysts
Posterior lobe cell types
Pituicytes - like astrocytes in the CNS, nourishes neurosecretory axons
Herring bodies: stores granules at the terminal ends of axons
Pituitary embryology
anterior from Rathke’s pouch, an invagination of oral ectoderm
Posterior from neuroectoderm, specifically, cells in the floor of the third ventricle
Testosterone functions
Growth of long bones during puberty Muscle growth with puberty, increase in muscle strength Stimulates red cell production Stimulates prostate growth Improves energy, cognition and mood Libido, nocturnal erections Growth of pubic, axillary, beard, chest, abdominal and back hair Growth of larynx with voice deepening
Sex hormone changes with age in men
Free and total testosterone decrease with age
70 yo: 66% of 30s
SHBG increases with age
DHEA decrease with age
Sex hormone changes with age in women
Adrenal androgen production decreases from age 30-60, then ver slowly
SHBG increased in 60s and 70s
Reduction of adrenal precursors of testosterone may be more relevant to women because they account for at least 50% of testosterone activity in cells
Large variation in ovarian androgen production in the 50s and onwards
Signs of testosterone deficiency
Early: fine body hair, smooth skin
Later: loss of body hair, softer beard, smaller and softer testes, small prostate, gynecomastia
Prolonged and severe: testes can become smaller and have a more rubbery consistency
Psychological: lack of energy, irritable mood, less assertive
Sexual: no nocturnal erections, loss of libido
Orgasms delayed with lower intesity, minimal ejaculate
(visually-induced erections are NOT dependent on testosterone)
Testosterone replacement therapy risks
Men: CV harm when given to older men (many with chronic disease)
women: some women with high levels of androgen are prone to CV disease, insulin resistance and metabolic syndrome
GH secretion characteristics
large amount (0.4 mg)/day high in newborns, tapers off in old age pulsatile (episodic) - most prominent during puberty - amplitude and frequency regulated by the hypothalamus
Involvement of Nor and Ach in GH response to hypoglycemia
GH secretion stimulated by deficiency of energy substrate
Glucose-sensitive central neurons activate GHR-secreting neurons in the arcuate nucleus, inhibit SS-secreting neurons in the PVN
Involvement of Nor and ACH in GH response to sleep
Surge of GH secretion shortly after the onset of slow wave sleep
- men: nocturnal surge constitutes the bulk of GH secretion
- women: nocturnal surge constitutes only a fraction of GH secretion
Mechanism of surge unknown, but reduced cortisol, decreased SS secretion or hypersecretion of GHRH could all contribute
GH feedback
short: hypothalamus: stimulate SS, inhibit GRH
Long: IGF1 stimulate SS, inhibit GRH, inhibit GH
GH binding proteins
40-45% of circulating human GH bound to high-affinity glycoprotein
is the soluble form of the extracellular domain of the GH receptor
function: reduce rate of degradation of GH, acts as a reservoir for GH
Jak-Stat system
JAK: janus kinase - tyrosine kinase
STAT - signal transducers and activators of transcription
1) absence of GH binding: receptor present as a dimer with JAK constitutively bound
2) GH binds to one molecule of the dimer, inducing the second receptor to bind to a different portion of GH
3) JAK molecules dimerize, cross phosphorylation of the JAK molecules (–> P JAK)
4) receptor tyrosines are phosphorylated by P-JAK
5) regions in the receptor phosphorylated by P-JAK are recognized by SH2-domains in intracellular signalling molecules, mosti mportantly STAT molecules. STATs phosphorylated by P-JAK
IGF1
Production in liver stimultaed by GH
Muscle: increase aa transport, protein syntehsis
Adipose: increase lipolysis
