Hypothalamus and Pituitary Flashcards
What is the function of the hypothalamus and pituitary glands?
The hypothalamus is responsible for direct control of the endocrine system through the pituitary gland
Where is the hypothalamus?
In the brain, below the thalamus
Where is the pituitary gland?
The pituitary is located at the base of the brain, just below the hypothalamus
How are the hypothalamus and the pituitary gland connected?
Through the pituitary stalk
Describe the structure of the pituitary gland
Small pea-sized gland below brain
Consists of 3 parts:
- Anterior lobe (adenohypophysis)
• glandular tissue, controlled by humoral releasing peptides from hypothalamus (via hypothalamo-hypophyseal portal system)
- Posterior lobe (neurohypophysis)
• neural tissue, made up of nerve-endings of neurones with cell bodies in the hypothalamus
- Intermediate lobe (pars intermedia) (not distinct in humans)
• glandular tissue, alternative processing of proopiomelanocortin (POMC)
Which part of the pituitary gland is not distinct in humans?
The intermediate lobe
Describe the hierarchy of the endocrine system
The hypothalamus releases hormones into the hypothalamo-hypophyseal portal system
These hormones act on the anterior pituitary, causing the release of trophic hormones
These trophic hormones pass the the circulatory system to their target organs, where they cause a response.
The target organs release hormones, which act as a negative feedback impulse, either directly; by acting on the anterior pituitary, or indirectly; by acting on the hypothalamus
Describe the release pathway of GnRH
The hypothalamus releases GnRH into the hypophyseal
portal system.
The GnRH binds to receptors on the anterior pituitary, and stimulates the release of LH and FSH.
LH and FSH passes through the bloodstream to the gonads, where they stimulate the release of sex steroids
Describe the release pathway of TRH
The hypothalamus releases TRH into the hypophyseal
portal system.
The TRH binds to receptors on the anterior pituitary, and stimulates the release of TSH.
TSH passes through the bloodstream to the thyroid, where they stimulate the release of sex T3 and T4
Describe the release pathway of CRH
The hypothalamus releases CRH into the hypophyseal
portal system.
The CRH binds to receptors on the anterior pituitary, and stimulates the release of ACTH.
ACTH passes through the bloodstream to the adrenal glands, where they stimulate the release of corticosteroids
Describe the release pathway of GHRF
The hypothalamus releases GHRF into the hypophyseal
portal system.
The GHRF binds to receptors on the anterior pituitary, and stimulates the release of GH.
GH passes through the bloodstream to the body tissues, where they stimulate growth
Describe the methods by whi hormone release is controlled
Direct negative feedback (where negative feedback acts directly on the anterior pituitary)
Indirect negative feedback (where negative feedback acts on the hypothalamus, and the hypothalamus acts on the anterior pituitary)
What are the types of endocrine disorders?
Primary
Secondary
Tertiary
What are primary endocrine disorders?
Lesion is on the endocrine organ - direct effect on hormone production, leading to pathological changes in metabolism
What are secondary endocrine disorders?
Secondary disorders occur when the endocrine organ is affected by lesions in another tissue. This is usually the pituitary, as it produces trophic hormones which control the activity of most of the endocrine organs
What are tertiary endocrine disorders?
-Hypothalamus-releasing factors control release of trophic hormones by the pituitary.
Lesion in the hypothalamus causes dysfunction of the pituitary, which causes dysfunction of an endocrine organ.
What is negative feedback?
The production of most hormones is controlled by a negative feedback loop. e.g. TSH stimulates thyroid hormone production, thyroid hormone inhibits TSH production.
What hormones are released by the anterior pituitary gland?
GH Prolactin TSH FSH LH ACTH β-lipotrophin
What is the function of GH?
Somatomedin synthesis, hence growth stimulation
Metabolic regulation
What is the function of prolactin?
Lactation
What is the function of TSH?
T3 & T4 synthesis & release
What is the function of FSH?
Oestrogen synthesis
Oogenesis
Spermatogenesis
What is the function of LH?
Ovulation
Corpus luteum (progesterone production)
Testosterone synthesis
What is the function of ACTH?
Glucocorticoid synthesis & release
Pigmentation (or αMSH)
What is the function of β-lipotrophin?
Precursor of endorphins
Describe the cycle of hormone release
Many pituitary hormones are secreted cyclically
- Circadian rhythms observable e.g. in cortisol are due to circadian variation in release of ACTH
Why is it important to know the cycles of hormone release?
When samples are collected, the time of day that they are collected needs to be noted.
How large is GH?
191 aa protein hormone
What hormones control the release of GH?
GNRH
Somatostatin
What diseases result from excessive GH production?
Gigantism (children)
Acromegaly (adults)
What diseases result from deficient GH production?
Growth retardation (children) Fatigue/reduced muscle strength (adults)
What are the metabolic actions of GH?
Increased lipolysis (ketogenic)
Increased hepatic glucose production (diabetogenic)
Increased protein synthesis (anabolic)
What is the function of somatostatin?
Inhibits GH
Inhibits TSH
Inhibits Gastrin, Insulin, Glucagon (paracrine - produced by islet d-cells)
How is assessment of GH disorders complicated?
Complicated by cyclical secretion
What is the normal GH level?
> 20 mU/l
How can GH deficiency be detected?
Normal is >20 mU/l - less during sleep or after exercise indicates possible deficiency
Perform insulin hypoglycaemia (glu < 2.2 mmol/l) test – inject short-acting insulin in clinically controlled conditions
GH increases over 20 mU/l – no deficiency
No stimulation - GH deficiency diagnosed
How can GH excess be detected?
GH may be measured by oral glucose tolerance test (OGTT)
GH normally suppressed by glucose
Not suppressed if produced by tumour
How can GH excess be treated?
GH excess usually due to pituitary adenoma
Surgery/radiotherapy
Octreotide/bromocriptine
How large is prolactin?
198 aa protein
What is the function of prolactin?
Stimulates lactation
What is hyperprolactnaemia?
Excess prolactin in the blood >600 mU/l
What causes hyperprolactinaemia?
Usually due to prolactinoma
What can hyperprolactinaemia cause?
Inhibits GnRH pulsatile release from hypothalamus
Causes infertility (impotence or amenorrhoea)
What can cause hypopituitarism ?
Tumours Trauma Infection, Hypothalamic disorders Iatrogenic (e.g. treatment of tumours)
How can hypopituitarism be assessed?
Using anterior pituitary function test:
- Assay resting glucose; ACTH/cortisol; FSH; LH; TSH; T4; GH; testosterone/oestradiol
- Assay following bolus of TRH, GnRH and insulin ~every 15 mins for next 2h
Sub-normal response indicates hypopituitarism
What is the precursor of ACTH?
POMC (Proopiomelanocortin)
What is POMC a precursor of?
ACTH
MSH
β-endorphin (but not enkephalins)
β-lipotropin
How is POMC processed in the anterior lobe of the pituitary?
Cleaved by PC1 to produce ACTH and β-lipotropin
How is POCM processed in the Intermediate Lobe of the pituitary/ Hypothalamus
Cleaved by PC1 to produce ACTH and β-lipotropin
ACTH then cleaved by PC2 to produce α-MSH and CLIP
β-lipotropin is cleaved by PC2 to produce γ-lipotrophin and β-endorphin
CLIP and γ-lipotrophin are then trimmed by exopeptidases to produce βCT and β-MSH
Where is β cell tropin produced?
Neurointermediate (NIL) pituitary
What is the function of β cell tropin?
Potentiator of GSIS (and amylin secretion)
- potent monophasic effect at low glucose (ED50 ~ 20 pM)
- increased biphasic effect at high glucose
What is the effect of β cell tropin in diabetics?
β CT potentiates biphasic response to high glucose
How many melanocortin receptors are there?
5
What are the roles of the different melanocortin receptors?
MC1R, MC2R and MC5R have established roles in pigmentation in the skin, adrenal steroidogenesis and thermoregulation respectively
MC3R and MC4R expressed in brain
- role in feeding modulation - k/o leads to obesity (hypothalamic POMC expression modulated by leptin)
How is ACTH release controlled?
Controlled by CRH (CRF)
What causes Cushing’s Disease?
Increased ACTH release due to tumour causes increased corticosteroid release, leading to Cushing’s Disease
What is the difference between Cushing’s Syndrome and Cushing’s Disease?
Cushing’s Disease is caused by increased ACTH release due to tumour causes increased corticosteroid release
Cushing’s Syndrome if increased corticosteroid due to
other causes
How can Cushing’s Disease be tested for?
Dexamethasone (synthetic glucorticoid) suppression test for Cushing’s disease (confirmed of plasma cortisol is above reference range - ~200mmol/l)
What causes Addison’s Disease?
A primary defect in corticosteroid production leads to loss of inhibitory feedback on CRH/ACTH secretion, hence overproduction of ACTH - also causes increased pigmentation
How can Addison’s Disease be tested for?
Administering Synacthen (ACTH1- 24; “Short ACTH”)
Addison’s Disease confirmed if patient’s plasma cortisol level below reference range after 60 minutes
What hormones are released by the posterior pituitary hormone?
Oxytocin
Vasopressin
How are posterior pituitary hormones produced?
Synthesised in hypothalamus and released from nerve endings in posterior pituitary
What is the function of oxytocin?
Control of uterine contractility and milk release
How large is oxytocin?
9aa protein
Give an example of positive feedback
Oxytocin release:
- suckling causes increased stimulation of afferent nerves from breast
- causes increased pituitary secretion of oxytocin
- causes increased lactation - more suckling “letdown reflex”
What is the function of vasopressin?
Controls water & mineral balance
How is release of vasopressin controlled?
Increased osmolality at hypothalamus - increased secretion
Decreased osmolality at hypothalamus - decreased secretion
What can a deficiency of vasopressin cause?
Diabetes insipidus
