Endocrinology Flashcards
How does the Mullerian duct develop
Invagination of the intermediate mesoderm
Describe male sexual characteristic developement
Wolffian ducts persist (epididymis, vas deferens and seminal vesicles) - male internal reproductive organs
Male external genitalia
Describe female sexual characteristic developement
Mullerian ducts persist (uterine tubes, uterus, cervix and upper 1/3 of the vagina)- female internal reproductive organs
What is N45a1
encodes steroidogenic factor 1 - critical regulator of reproduction, upregulates transcription of SOX9 gene
What is dmrt1
located at end of 9th chromosome, dose sensitive transcription factor protein that regulates sertoli cells and germ cells (2 copies required for normal sexual development
What is SRY gene
adjacent to the centromeric portion of the PAR1 region (close to region of homology so may be duplicated/deleted)
SRY is sufficient to confer testes formation in a female
What is SOX9
important for teste formation so males require 2 copes, has capability to bind and regulate itself. Gene on chromosome 17
What is DAX1
inhibitor factor. Gene on X chromosome. Represses teste development, dose sensitive. Duplications lead to DSD in XY individuals
What is required for ovary formation
requires presence of germ cells and two X chromosomes
Wnt4;ctnnb1 - found on chromosome 1, promotes female sex development and regress male sex development
When does sex differentiation occur
8 weeks
How does male sex differentiation occur
Male: AMH (prevents Mullerian structures from development), testosterone stabilise Wolffian structures
Testosterone converted into DHT - promotes the development of genital tubercles, labioscrotal folds and urogenital sinus into penis, scrotum and prostate
What happens in the absence of male hormones
Wolffian structure regress
What does the genital tubercle become in females
Clitoris
What does the urogenital sinus become in females
Lower vagina
What do the labioscrotal folds become in females
Vuvlar
What is Klinefelter
47, XXY
Normal at birth, higher incidence of undescended testes, tall stature, small pea-sized testes, lack of secondary characteristics, gynaecomastia, infertility
What occurs with SRY translocations
Present after puberty with short stature, gynaecomastia, small testes, fertility issues
Male gender identity, treated with testosterone
What occurs with 5-alpha reductase deficiency (generates DHT)
Internal strctures male, variable appearance of external genitalia at birth, during puberty increased androgen levels lead to virilisation (masculinization) of external genitalia
What hormones at tyrosine derivatives
dopamine, adrenaline, thyroxine
How many aa is GnRH
10
How many aa is GHRH
44
How many aa is prolactin
198
What hormone is linked by disulphide bridge
Insulin
What are glycoprotein hormones
Alpha and beta chains with carbohydrate
Alpha chain - species specific
Beta chain - hormone specific
Give examples of glycoprotein hormones
LH, FSH, hCG, TSH
What happens with pulsatile release of GnRH
Release of LH and FSH (vice versa for sustained release)
What are steroid hormones made from
Cholesterol
What does PLC do
Breaks down membrane phospholipid
What does DAG do
Increase PKC
What does IP3 do
Release Ca2+
What does PKC do
Increase protein phosphorylation
Where is GLUT4 found
Adipose and striated muscle tissue
Describe insulin binding
Ligand binds to alpha chain of the IR ectodomain
Leads to auto phosphorylation of various tyrosine residues within the intracellular TIC domain of the beta chain
Facilitates the recruitment of special adapter protein such as IR, SH2-b, APS and protein phosphatases
Describe steroid receptor mechansim
Er alpha - oestrogen receptor alpha activates transcription
Er beta - oestrogen receptor beta inhibits transcription
HSP (heat shock protein, prevents interaction with DNA) - dissociated and the activated receptor-ligand complex translocated into the nucleus
Steroid receptor often form dimers
Complex acts as a transcription factor
Where are catecholamines stored
Secretory granule or vesicle, circualte in free form
Where are thyroid hormones stored
Formed within thyroglobulin, stored in colloid. Circulate in bound form
Where are proteins stored
Circulate largely in free form
Stored in secretory granule, released by exocytosis triggered by Ca2+
Contents released and granule recycled
Which hormones are hydrophilic
Catecholamines and peptide hormones, do not associate with plasma protein
Where are steroid hormones stored
Formed from cholesterol, multi enzyme biosynthesis
Circulate mainly in bound form
Not stored
Biosynthesis involves mitochondria and smooth ER
Describe anterior lobe of the pituitary
Pars distalis, pars tuberalis - endocrine cells
What hormones are produced in the anterior pituitary and from what cells
Corticotroph - ACTH Gonadotroph - FHS, LH Lactotroph - Prolactin Somatotroph - GH Thyrotroph - TSH Melanocyte stimulating hormone
Describe posterior lobe of the pituitary
Pars nervosa, infundibulum (pituitary stalk) - neurocrine cells
List the hypothalamic hormones
Corticotropin releasing hormone Gonadotropin releasing hormone Prolactin releasing hormone - TRH Prolactin inhibitory factor - dopamine Growth hormone releasing hormone GH release inhibiting hormone (somatostatin) Thyrotropin releasing hormone
Describe hormone production in males
Hypothalamus (GnRH) ->Anterior pituitary (FSH and LH)
FSH -> sertoli cells facilitate spermatogenesis ->production of inhibin to inhibit secretion of LH and FSH
LH ->leydig cells (increased production of testosterone)-> negative feedback to anterior pituitary and hypothalamus
LH and FSH stimulate spermatogenesis and testosterone secretion by the testes
What does prolactin do
Increased secretion during pregnancy and lactation
Release controlled by hypothalamic hormones
In pregnancy promotes additional breast development
Post-partum stimulates milk production
What releases and what inhibits prolactin
Prolactin inhibitory factor - dopamine
Prolactin releasing factor - TRH
Describe posterior pituitary hormones
Synthesised with neruophysin as precursor in cell bodies in supraoptic nucleus and paraventricular nucleus of hypothalamus
Associated with neurophysin I (OXY) or neurophysin II (AVP)
Describe oxytocin’s mechanism of action
Suckling -> nipple mechanoreceptors -> hypothalamus -> posterior pituitary í oxytocin -> stimulation of myoepithelial cells -> milk ejection
How does AVP maintain blood pressure
Fluid balance - increased water re-absorption
Blood vessels - vasoconstriction
What does hyperprolactinaemia cause
Galactorrhoea - milk secretion from breast
Gynaecomastia - excess breast growth n males
Infertility - males and females
What is the treatment for hyperprolactinaemia
D2 agonists (cabergoline, bromocriptine)
How is infertility treated
Often caused by hyperprolactinaemia
Prolactin causes milk production and suppresses menstrual cycle
Describe GH synthesis and release
Partly acts by GH receptor and partly by synthesis of IGF in the liver
Release controlled by hypothalamic hormones (GHRH, somatostatin)
GH and IGF induce negative feedback
What are the actions of growth hormone
Growth of long bones until fusion of epiphyses Increase in size of viscera Anti-insulin effects Metabolic effects related to growth Anabolic for protein Catabolic for fats and carbohydrates
What factors stimulate GH secretionn
Physiological: exercise, stress, sleep, postprandial glucose decline
Pharmacological: drug induced hypoglycaemia, aa infusions, small peptide hormones, monoaminergic stimuli
What happens with GH hypersecretion
Gigantism before fusion of epiphyses
Acromegaly (typically enlargement of hands and feet) after fusion of epiphyses - greatly enhanced basal levels
What is the treatment of GH hypersecretion
Trans-shpenoidal surgery Bromocriptine/carbegoline - D2 agonists Octreotide - long acting somatostatin Lanreotide - analogues SSTR2 agonists Pasireotide - SSTR5 agonist
What happens with GH hyposecretion
Short stature before fusion of epiphyses
Adult growth hormone deficiency after fusion of epiphyses
What is the treatment for GH hyposecretion
Treatment with recombinant hGH (somatropin) or recombinant HIGF-1 (mecasermin)
