L12 – Physiology of Pituitary Hormones Flashcards
Summarize the flow of neurohormones from hypothalamus to anterior pituitary?
dorsal medial, ventral medial, infundibular nuclei + PVN secrete neurohormones into
the Hypophyseal portal system:
primary capillary plexus @ median eminence
» secondary capillary plexus
» Adenohypophysis
Summarize the flow of neurohormones from hypothalamus to posterior pituitary?
paraventricular nucleus (PVN) and supraoptic nucleus (SON) secrete neurohormone
> > axon directly to posterior pituitary
stored in Herring bodies
Define the neurohormones secreted by the arcuate nucleus and their effect on anterior pituitary cells?
1) GH-releasing hormone (GHrH)»_space; Somatotrophs»_space; Growth hormone
2) Gonadotropin releasing hormone (GnRH)»_space; Gonadotrophs»_space; FSH and LH
3) (-) Dopamine»_space; Lactotrophs»_space; Prolactin
Define the neurohormones secreted by the PVN and their effect on anterior pituitary cells?
1) Corticotrophin releasing factor»_space; corticotrophs»_space; Adrenocorticotropic hormone
2) Thyrotropin releasing hormone»_space; Thyrotrophs»_space; TSH
Define the neurohormones secreted by the PVN
and SON and their effect on posterior pituitary cells?
PVN and SON:
Release Vasopressin and Oxytocin
Define the stimulating and inhibitng factors of Growth hormone/ somatotropin?
Stim = growth hormone-releasing hormone (GHRH) from arcuate nucleus»_space; negative feedback to GHRH neuron
Inhibited by somatostatin (SS) from periventricular nucleus
Summarize the direct and indirect pathways for Growth hormone effect?
Directly activate GH-receptor:
i) Muscle = protein synthesis
ii) Adipose tissue = lipolysis
iii) Block GLUT-4 on diff. tissue = decrease glucose uptake
Indirect:
Activate GH-R on liver: produce IGF-1 to Bone, cartilage:
- Chondrocyte proliferation, bone growth
Which hormone has antagonistic action to growth hormone?
Insulin
Increased blood glucose suppresses GH secretion
OGTT can be suppression test for GH
Describe the feedback control of growth hormone release?
Increased GH»_space; Increase stimulation of GH-R on liver»_space; Increase IGF-1 production:
- Suppress somatotrophs
- Stimulate release of Somatostatin from PVN
> > feedback decrease GH secretion
Define the cause of GH hypersecretion, related symptoms?
- Commonly tumour of somatotrophs in anterior pituitary
- Hypersecretion of GH = Acromegaly and Gigantism:
- Enlargement of organs
- CVD
- Hypertension
- DM (GH antagonize Insulin)
Define the cause of GH hyposecretion, related symptoms and treatment?
Cause: damage to hypothalamus/ pituitary or mutation in GH secretion regulation
Result: Dwarfism:
- Growth retardation
- Hypoglycaemia»_space; decreased energy
- Low BMD, low muscle strength
- Delayed puberty
Treatment: GH admin
Define the cause of GH unresponsiveness, treatment?
Laron Syndrome
Autosomal recessive: GH receptor mutation = insensitive to GH
Treatment = IGF-1 admin
Describe the rate of GnRH secretion from arcuate nucleus and the effects on gonadotropins?
GnRH = pulsatile secretion
High freq.= LH synthesis and secretion
Low freq. = FSH synthesis and secretion
Compare the effects of FSH and LH on gonads?
FSH = Gametogenesis (spermatogenesis and oogenesis)
LH = synthesis and secretion of sex steroids (Steriodogenesis)
Effect of FSH on male gonad? (3)
Stimulates testosterone-binding protein in Sertoli cells to help spermatogenesis (permissive effect)
Stimulates spermatogenesis
Increase production, secretion of inhibin = negative feedback to FSH secretion in anterior pituitary
Effect of FSH on female gonad?
Induces LH receptors expression on granulosa cells > ready for ovulation
Stimulates oogenesis
Increase production, secretion of inhibin = negative feedback to FSH secretion in anterior pituitary
Effect of LH on male gonad?
Stimulates steroidogenesis (testosterone) in Leydig cells of testis
Increase plasma testosterone = negative feedback pn FSH, LH and GnRH secretion
Effect of LH on female gonad? (4)
Stimulates steroidogenesis (testosterone) in theca cells of ovary»_space; enzymatically modified by granulosa cells into estrogen
Estrogen stimulates oogenesis, follicular development
Terminates 1st meiosis = forms secondary oocyte
Causes ovulation = forms corpus luteum (produces progesterone)
Describe how LH self regulates secretion in females?
Increase plasma estrogen = feedback inhibition on FSH, LH, GnRH
List 2 causes of hypergonadotropism?
- Pituitary tumor of gonadotropin
2. Ectopic GnRH-producing tumors of the lung and liver cell lines
List 2 causes of gonadotropin deficiency leading to hypogonadism?
1) Hyperprolactinemia»_space; decrease GnRH production
2) Genetic mutation
i) GnRH neuron development (Kallman’s syndrome)
ii) GnRH receptor
iii) β-subunit of gonadotropin gene
Define the cause and effect of Kallmann syndrome?
X-linked / autosomal recessive
GnRH-secreting neurons are congenitally absent
No puberty, infertile
Which hormone secreted by the anterior pituitary is affected by dopamine differently than the rest?
Prolactin: Tonically Inhibited by dopamine from hypothalamus
Describe the hypothalamic control to stimulate prolactin release?
1) Neurogenic stimuli (breast feeding) activate ANS»_space; inhibit dopamine release at hypothalamus»_space; Reduce tonic inhibition on lactotrophs to secrete prolactin
2) Physiological stimuli: high estrogen due to pregnancy»_space; stimulate anterior pituitary directly»_space; secrete prolactin
Describe the effect of prolactin on mammary glands?
Prolactin bind to PRL-R (tyrosine kinase receptor)
> > receptor dimerize»_space; activate JAK- STAT5 for gene transcription:
i) Growth and development of mammary gland for lactation
ii) Milk production by alveolar epithelial cells (galactopoiesis)
Describe how prolactin inhibits lactating women from premature pregnancy?
Prolactin bind to receptors on afferent neurons of hypothalamic GnRH neurons
> > reduce stimulation of GnRH neurons
decrease GnRH = decrease FSH and LH from pituitary gonadotrophs
List 3 pathological causes of hyperprolactinemia?
Prolactinomas at pituitary
Hypothalamic, pituitary stalk disorders: e.g. loss of dopamine inhibition on PRL
Ectopic prolactin secretion from other tumors at other parts of body
Effects of hyperprolactinemia on male and female?
- Abnormal lactation (galactorrhea)
- Hypogonadism, infertility (inhibit GnRH)
Female:
Anovulation (lack of ovulation)
Amenorrhea (lack of menstruation)
Male:
Low testosterone level = lack of sex desire, erectile dysfunction
Enlargement of breast tissue
Treatment options for hyperprolactinemia?
Prolactin receptor blocker
Dopamine agonist
Vit B6
Cause and effect of Sheehan syndrome?
blood loss and hypovolemic shock during and after childbirth
> > postpartum pituitary necrosis
> > cannot release prolactin/ breastfeed
Define the precursor of ACTH?
proopiomelanocortin (POMC): cleaved into (not all):
- ACTH
- Endorphin
- Melanocyte-stimulating hormone
- Corticotropin-like intermediate peptide (CLIP)
Describe the trigger and effect of ACTH?
Trigger = Corticotropin-releasing hormone from PVN»_space; bind to CRH-R
Effect = increase production of POMC and release of ACTH at corticotrophs»_space; stimulate adrenal cortex hormone production
Describe the effect of ACTH on its target organ?
Binds to MC2R ( melanocortin receptors) at adrenal cortex» transcription of genes:
i) increase cholesterol uptake by adrenal cortical cells + cell growth
ii) Activate steroidogenic enzymes for steroidogenesis»_space; make cortisol and androgens
Describe the normal feedback regulation of ACTH?
ACTH > adrenal cortex > cortisol
1) Cortisol negatively feedback inhibit release of Corticotropin-releasing hormone (CRH) in hypothalamus
2) Suppress POMC production and ACTH release in corticotrophs at ant. pit.
Describe the effects of extremely high plasma ACTH?
bind with low affinity to activate MC1R expressed in melanocytes of skin, hair follicles
produce, dispense brown/black melanin pigment»_space; hyperpigmentation (skin darkening)
Define difference between primary and secondary adrenal insufficiency?
Primary = Adrenal cortex is dysfunctional: high ACTH and CRH
Secondary = Either hypothalamus or Pituitary is dysfunctional
Define ACTH deficiency?
Failure of hypothalamus to stimulate pituitary ACTH production: Low CRH and ACTH
Classify as secondary adrenal insufficiency
Which 2 conditions mimic the symptoms of ACTH deficiency (secondary adrenal insufficiency)?
Primary adrenal insufficiency (i.e. Addison’s disease)
Hereditary Mutation in the MC2R gene
High CRH, ACTH, but low cortisol. Which type of adrenal insufficiency?
Primary
High CRH, Low ACTH, Low cortisol .Which type of adrenal insufficiency?
Secondary, pituitary disease
Low CRH, Low ACTH, Low cortisol .Which type of adrenal insufficiency?
Secondary, hypothalamus diease
List 2 causes of over-production of ACTH?
Adenoma of corticotrophs at pituitary
Ectopic CRH/ACTH production in some fastgrowing tumors (e.g. oat cell carcinoma of the lung)
Diff. between Cushing disease and Cushing syndrome?
Disease = excessive secretion of ACTH from the anterior pituitary gland (secondary disorder)
Syndrome = primary disorder in adrenal cortex = symptoms that occur due to high cortisol levels
Compare structure of glycoprotein hormones secreted by anterior pituitary?
FSH, LH, TSH
Common a- subunit
specific B- subunits
Describe the trigger and effect of TSH release?
PVN»_space; Tyrotropin-releasing hormone (TRH)»_space; Pituitary thyrotropes»_space; TSH
TSH receptor on thyroid follicular cells»_space; thyroidal gene expression:
1) Thyroid cell growth and differentiation
2) T3, T4 production
Describe the TSH regulation?
TSH > thyroid follicular cells > T3,T4
i) T3 inhibit pituitary thyrotrope: decrease synthesis of TSH β subunit, TSH secretion
ii) T3 inhibit TRH synthesis in hypothalamus
Compare the structure between Vasopressin and Oxytocin?
Both 9a.a. long, only differing in 2 a.a.
Source of Vasopressin and Oxytocin?
Magnocellular neurons of PVN and SON
> > hypothalamo/ hypophyseal tract to the posterior pituitary, carry by neurophysin
> > Stored in Herring Bodies at terminal axon
Describe the release mechanism of Vp and Oxytocin?
Stimuli > depolarize magnocellular neuron
> > AP propagate down hypophyseal tract to terminal axon
> > Depolarization = open Ca channels to increase [Ca] intracellular
> > Exocytosis of Herring bodies and release Vp/ oxytocin into fenetrated capillary
Summarize the effects of Vp?
Receptor = GPCR:
1) V1aR is coupled to Gαq protein: vascular smooth muscle»_space; vasoconstriction
2) V2R is coupled to Gαs protein: Renal collecting ducts: Trafficking of AQP2 to apical membrane for water reabsorption
Summarize the effects of Oxytocin?
1) Positive feedback on uterus myometrium contraction during labor
2) Contraction of myoepithelial cells in mammary gland for milk let-down during breastfeeding
Disease caused by Vp insufficiency?
diabetes insipidus
Kidney cannot concentrate urine adequately
Diff. between central and nephrogenic Diabeter insipidus?
A. Central diabetes insipidus (CDI): defect of vasopressin production / release
B. Nephrogenic diabetes insipidus (NDI): kidney cannot respond to vasopressin by producing concentrated urine
What causes Nephrogenic diabetes insipidus (NDI)?
a. Mutation in V2R
b. Genetic defect in the AQP2 gene
3 causes of excessive vasopressin?
Inappropriate ADH secretion:
1) Certain cancers with ectopic Vp production
2) Heart failure with aberrant baroreceptor activity
3) Diseased hypothalamus with slow leakage of Vp
Symptoms and signs of Excessive Vp?
- hypotonic / dilutional hyponatremia
- Mild to moderate: headache, nausea, muscle weakness
- Advanced: cerebral edema = confusion, hallucination
- Grave: seizures, coma, death
