Endocrinology Flashcards
What are the characteristics of the hormone super families?
Peptides- stored for a day, secreted via exocytosis, lasts for mins-hours, works for mins-hours
Steroids- stored for mins-hours, secreted by diffusion, lasts for hours, works for hours-day
Thyroid hormones- stored for weeks, secreted by proteolysis, last for days, work for a day
Catecholamines- stored for a day, secreted by exocytosis, last for sec-mins, work for seconds
Describe peptide hormones
Water soluble
Largest in number
Normally proteolytic ally cleaved to form the active hormone
Stored in vesicles- for immediate release
Made as preprohormones with a signal peptide and ‘inactive’ fragment
Describe amino acid derivatives as hormones
Thyroid hormones from tyrosine in the thyroid gland
Describe steroid hormones
Lipophilic- easily pass through the plasma membrane
Includes sex hormones, glucocorticoids, thyroid hormone and vitamin D
Not stored- produced on demand
Produced in adrenal cortex, corpus luteum and ovaries in women and testes in men
Starts from cholesterol (transported into mitochondria by StAR)➡️ pregnenolone by P450cc through 2 hydroxylase and one cleavage reaction
List the endocrine glands
Hypothalamus Pituitary Thyroid Parathyroid a Adrenals Pancreas Ovary Testes (Heart, intestines, skin, liver, kidney)
What is a hormone receptor?
Bind the hormone specifically
Be able to detect it and high enough affinity in blood amount related molecules
The receptor must be only in specific tissues?
Must be saturable
Reversible
Must mediate some biological response
Describe intrinsic tyrosine kinase activity
An enzyme that has the intrinsic ability to transfer a phosphate group to a tyrosine residue
Eg. Epidermal growth factor (EGF) receptor 1-4, ligand induced dimerisation, signal transduction processes-
Eg. Dimerization➡ transphosphorylation➡ GRB➡ SOS➡ Ras(+GTP)
Insulin receptor- PI 3-kinase
Describe recruited tyrosine kinase activity
JAK-STAT
Ligand binds (cytokines) JAK recruited to pohosphorylatr the receptor which then recruits STAT
STAT is phosphorylate - now active and localises to the nucleus to affect transcription
Describe the G protein coupled receptor
7-pass transmembrane protein
Act via an intracellular second messenger system eg. cAMP, inositol, IP3, diacylglycerol (DAG)
The G proteins are heterotrimeric- alpha, beta and gamma subunits
Activation of a receptor causes a confirmation change in the alpha subunit allowing ADP exchange for ATP releasing the alpha unit and the beta-gamma complex forms a functional unit
These act as second messengers eg. DAG activates PLC➡ Ca➡ calmodulin➡ calmodulin-activated kinases
And PKC
Results in phosphorylated target proteins
Describe steroid hormone receptors
Few with cell surface receptors
Most receptors are in the cytoplasm and as a complex binds to a gene target
Type 1 receptors- work as homodimers eg. Glucocortoid, mineralcorticoid, progesterone, oestrogen and androgen
Active transport to nucleus AMD bind to sequence es of DNA called hormone response elements (HREs)
Type 2 receptors- heterodimerise with RXR eg. VDR, RAR, TR
Retained in nucleus
When not ligand bound in complexes with co-repressor proteins, ligand binding recruits co-activator proteins
Described the structure of nuclear receptors
Conserved
AF1 at the N terminal, DNA binding in the middle and AF2 near the C terminal
AF1+2 work synergistically for transcriptional activation
Describe HRE
Hormone response elements Monomeric- A/T rich region 5' to half-site Dimeric- Pal HRE- palindrome or inverted DR HRE- direct repeat IP HRE- inverted palindrome Recognised by P-box on zinc fingers
Describe the orgnaisation of the hypothalamus
A collection of brain nuclei or centres which have impoortnat control and integrative functions
Important for homeostasis and primitive functions
Controls autonomic functions via brainstem autonomic centres
Controls endocrine function via the pituitary gland
List some hypothalamic hormones
Thyroid releasing hormone- TRH Gonadotrophin Releasing hormone- GnRH Growth hormone releasing hormone- GHRH Somatostatin Corticotropin releasing hormone- CRH Dopamine Small peptides Release is pulsatile inducting rapid effects on the release of cognate anterior pituitary hormone
Describe the pituitary gland
Anterior pituitary hormones regulated by secreted hypothalamic factors
Posterior pituitary hormones synthesised in hypothalamus and transported via neural projections
Structurally continuous with the hypothalamus by the pituitary stalk
List the anterior pituitary cell types and the hormone they secrete hormones
Thyrotroph- thyroid stimulating hormone (TSH)
Corticotroph- adrenocorticotrophic hormone (ACTH)
Gonadotroph- luteinizing hormone and follicle stimulating hormone (LH/FSH)
Somatotroph- growth hormone (GH)
Lactotroph- prolactin (PRL)
Single chain hormones- PRL, GH
Two chain glycoproteims: common alpha + unique beta- TSH, LH, FSH
List the posterior pituitary hormones
ADH
Neurophysins
Oxytocin
What is POMC?
A large precursor polypeptide that is ther source of several important biologically active substances including:
ACTH
Gamma-MSH
Beta-LPH (corticotroph cell)➡ gamma-LPH+ beta-endorphin (brain)
What are the different types of secretion?
Constitutive
Regulated
Pulsatile
Diurinal
Describe thyroid stimulating hormone
TSH is made in thyrotrophs in the anterior pituitary is response to pulsatile TRH release in the hypothalamus
Pituitary failure can result in secondary hypothyroidism
Pituitary tumour can result in secondary hyperthyroidism
Describe gonadotrophins
LH and FSH
Made by gonadotrophs (most mame both, some only make one) in the anterior pituitary on response to GnRH
Regulate testosterone biosynthesis and spermatogenesis in the testes
Regulate menstruation and fertility in the ovary
Both act through cell membrane receptors coupled to Gs proteins➡ cAMP➡ PKA
Describe adrenocorticotropic hormone
ACTH Synthesised by corticotrophs in the anterior pituitary
Stimulates GPCR coupled to cAMP
stimulates enzymes that convert cholesterol to cortisol or sex steroid hormones (eg StAR)
Describe prolactin
Made in lactotrophs- production increases during pregnancy due to increase in oestrogen
Inhibits its own release
Stimulates mammary gland development via DNA synthesis, epithelial cell proliferation, synthesis of lactose, casein, lactalbumin, free fatty acids
Maintains lactation via synergy with glucocorticoids, inhibited by oestrogen and progesterone
What is a prolactinoma?
Most common pituitary tumour
Interfere with HPG axis resulting in infertility, amenorrhoea, galactorrhoea
Treatment with dopamine agonists
Describe growth hormone
Released by somatotrophs
Pulsatile secretion
Stimulated by low glucose, exercise and sleep
Protein hormone carried by proteins
Release inhibited by somatostatin
Deficiency or resistance:
GH receptor mutations- laron syndrome dwarfism- treated with IGF1
GH deficiency- treated with recombinant hGH
Describe ADH
Nonapeptide suyntheised by the posterior pituitary
Packaged with the carrier protein neurophysin in secondary granules in the magnocellular neurones of the periventricular and supraptic nuclei
Acts in collecting ducts in the kidneys- aquaporins
Diabetes insipidus- posterior pituitary damage may reduce ADH and urine cannot be concentrated
Describe oxytocin
Synthesised in the posterior pituitary
Stimulates contraction of smooth muscle of the breast and uterus
Can be given to induce labour
Neuro-endocrine reflexes
