Metabolism - Session 11, Lecture 2

Location:  located at the base of the brain suspended from the hypothalamus by a stalk. It lies in a deep recess of the sphenoid bone (pituitary fossa).  Weighs g and is larger in females (effect of oestrogen on Lactotrophs).

 Portal system i.e. a vessel connecting two capillary beds located in separate tissues, (hypothalamus and in the anterior pituitary).  Superior and inferior hypophyseal A(from internal carotid A).

 Fusion between :  an up-growth of ectodermal cells from the roof of the primitive pharynx (buccal cavity) that forms the anterior lobe (adenohypophysis)  and a down-growth of neural tissue from the hypothalamus that forms the posterior lobe (neurohypophysis).

 TSH is produced in the Thyrotrophs.  ACTH produced in the Corticotrophs.  Growth hormone produced in the Somatotrophs.  LH and FSH are produced in the Gonadotrophs.  Prolactin is produced in the Lactotrophs

 The adrenal glands are a pair of multifunctional endocrine glands that cap the upper poles of the kidneys and lie against the diaphragm.  They are small in size and have a combined weight of 6-8 g (slightly less in the female).

 Cortex  Mineralocorticoids e.g. aldosterone (C21 steroid)  Glucocorticoids e.g. cortisol and corticosterone (C21 steroids) major steroidsproduced.  Androgens e.g. dehydroepiandrosterone (C19 steroid)  Medulla  Adrenaline (epinephrine)

1. Zona Glomerulosa. outermost zone secrete the mineralocorticoids (e.g. aldosterone) that regulate the body Na+ and K+ levels. 2. Zona Fasciculata. produce the glucocorticoids (e.g. cortisol) that have a number of important functions including the regulation of carbohydrate metabolism. 3. Zona Reticularis. the deepest cortical zone secrete glucocorticoids and small amounts of androgens (dehydroepiandrosterone)

 Cortisol is a member of the C21 steroid family  differ from other steroids in the number of C-atoms, presence of functional groups and distribution of C=C double bonds.

Steroid hormones are synthesised from cholesterol via progesterone in a series of enzyme catalysed reactions.

 ACTH or corticotrophin secreted from the corticotrophs controlling the release of cortisol.  The secretion of ACTH is under the control CRF, produced in the hypothalamus.  CRF is secreted in response to physical (temperature, pain), chemical (hypoglycaemia) and emotional stressors.  There is -ve feedback by glucocorticoids on both the hypothalamus & pituitary.

 ACTH is a 39 amino acid, single chain polypeptide hormone. The initial biosynthetic precursor is a large protein (~250 amino acids) called proopiomelanocortin (POMC).  Post-translational processing of POMC at different sites produces a range of biologically active peptides including ACTH, MSH (melanocyte stimulating hormone) and endorphins.  The MSH sequence of 13 amino acids is contained within the ACTH sequence in POMC giving ACTH some MSH-like activity when present in excess.

 ACTH has a short half-life in the circulation (~8min).  Peak plasma levels occur in the early hours of the morning and the lowest levels at the late evening.  ACTH is hydrophilic and interacts with high affinity receptors on the surface of cells in the zona fasiculata and reticularis.  The binding of ACTH to these receptors leads to activation of cholesterol esterase increasing the conversion of cholesterol esters to free cholesterol. It also stimulates other steps in the synthesis of cortisol from cholesterol.

 Over-secretion of ACTH causing increased pigmentation due to partial MSH activity.  Under secretion of ACTH produces symptoms related to the lack of glucocorticoids but not those related to lack of mineralocorticoids as aldosterone secretion is normal (not controlled by ACTH).

 As ACTH is a peptide hormone it acts on receptors on the cell membrane.  ACTH receptor is a type o melanocortin receptor (type 2), known as MC2( the corticotropin receptor).  This receptor uses cAMP as a 2 nd messenger.

 Cortisol, is lipophilic and must be transported bound to plasma proteins:  Transcortin (~90% )  the remaining ~10% being free and biologically active

 Cortisol can cross the plasma membranes of target cells and bind to cytoplasmic receptors.  The hormone/receptor complex then enters the nucleus to interact with specific regions of DNA.  This interaction changes the rate of transcription of specific genes and may take time to occur.

 amino acid uptake, protein synthesis & proteolysis in most tissues (not liver).  hepatic gluconeogenesis and glycogenolysis.  lipolysis in adipose tissue N.B. high levels of cortisol lipogenesis in adipose tissue.  peripheral uptake of glucose (anti-insulin).  direct effects on cardiac muscle, bone and the immune system.

 The adrenal medulla is, a modified sympathetic ganglion that synthesises various catecholamines including the hormone adrenaline (epinephrine) and the neurotransmitters noradrenaline (norepinephrine) and dopamine.

 CVS ( cardiac output, blood supply to muscle).  CNS( mental alertness).  CHO metabolism( glycogenolysis in liver and muscle).  lipid metabolism ( lipolysis in adipose tissue).

 Overproduction of adrenaline due to a tumour (Phaeochromocytoma), may be associated with hypertension, anxiety, palpitations,pallor, sweating and glucose intolerance.