Neuroendocrine Flashcards
Anterior Pituitary Gland (anterior lobe):
i. Hypothalamic-Pituitary-Growth Hormone Axis -> Growth
ii. Hypothalamic-Pituitary-Prolactin Axis -> Lactation
iii. Hypothalamic-Pituitary-Thyroid Axis -> Thyroid gland function
iv. Hypothalamic-Pituitary-Adrenal Axis -> Adrenal gland physiology
v. Hypothalamic-Pituitary-Gonadal Axis -> Sex Hormones & Reproduction
Posterior Pituitary Gland (Posterior lobe):
i. Antidiuretic Hormone (ADH) -> Water homeostasis, plasma volume & osmolality.
ii. oxytocin -> uterine contraction and lactation.
hypothalamus
It integrates neural signals from brain
⇒ converts those signals into chemical messages (largely peptides) which regulate the secretion of pituitary hormones
⇒ pituitary hormones alter the activities of peripheral endocrine organs.
The majority of hypothalamic releasing factors are secreted in a __________________
cyclical or pulsatile, rather than continuous, manner.
(1) Hypothalamic-Pituitary-Growth Hormone Axis
Somatotrophs of the anterior pituitary gland produce and secrete growth hormone.
-> insulin-like growth factors, especially insulin-like growth factor 1 (IGF-1) -> by hepatocytes in response to GH.
Factors that Increase GH secretion
• Environmental factors can Increase GH, such as:
- • Hypoglycemia
- • Sleep, exercise
- • Adequate nutritional status.
Endogenous biological inputs
- • Hypothalamic GHRH,
- • Sex steroids (during puberty)
- • Dopamine & Ghrelin
Ghrelin
endogenous growth hormone-releasing peptide
on a receptor that is distinct from the GHRH receptor.
The majority of ghrelin is secreted by gastric fundal cells during the fasting state
ANTERIOR PITUITARY GLAND CELL TYPE
- Somatotroph
- Lactotroph
- Thyrotroph
- Corticotroph
- Gonadotroph
Hypothalamic control of Anterior pituitary
- Through: hypothalamic-pituitary portal vascular system.
- FSH & LH
- GH
- Prolactin
- ACTH
- TSH
Hypothalamic control of Posterior pituitary
- Through: direct neural connection between hypothalamus & posterior pituitary
- ADH
- Oxytocin
Primary
underlying abnormality is in the target organ
Secondary
underlying abnormality is in the pituitary gland
Tertiary
underlying abnormality is in the hypothalamus
(1) Hypothalamic-Pituitary-Growth Hormone Axis.
- Somatotrophs of the anterior pituitary gland produce and secrete growth hormone.
- GH
- IGF-1
GH
- first expressed at high concentrations during puberty;
- it is secreted in a striking pulsatile manner ⇒ largest pulses usually occurring at night during sleep.
- Most of anabolic effects of GH are mediated by
⇒ insulin-like growth factors, especially insulin-like growth factor 1 (IGF-1)
⇒ a hormone released into the circulation by hepatocytes in response to GH.
IGF-1
- hepatocytes contribute the overwhelming majority of detectable IGF-1 in the circulation.
- IGF-1 is protein-bound and stable in the circulation for longer periods of time at steady concentrations.
- IGF-1 measurements represent an integrated surrogate for GH activity that is stable throughout the day
- > IGF-1 levels are a more appropriate tool than GH levels in screening for acromegaly.
Factors that Increase GH secretion
• Environmental factors can Increase GH, such as:
- • Hypoglycemia
- • Sleep, exercise
- • Adequate nutritional status.
- Endogenous biological inputs that promote GH release include:
- • Hypothalamic GHRH,
- • Sex steroids (during puberty)
- • Dopamine & Ghrelin
Ghrelin
- endogenous growth hormone-releasing peptide
- acts synergistically with GHRH to promote GH release, acting on a receptor that is distinct from the GHRH receptor.
- The majority of ghrelin is secreted by gastric fundal cells during the fasting state
Factors that Decrease GH secretion
Environmental factors can increase GH, such as:
- Hyperglycemia
- Sleep deprivation
- Poor nutritional status.
Endogenous biological inputs that promote GH release include
- Somatostatin
- IGF-1 & GH.
GH and IGF-1 replacement or stimulators
1) Somatropin
2) Somatrem
3) Sermorelin
4) Tesamorelin
5) Mecasermin
Growth Hormone Excess
1) Gigantism
2) Acromegaly
Gigantism
occurs if GH is secreted at abnormally high levels in children before closure of the epiphyses because increased IGF-1 levels promote excessive longitudinal bone growth
Acromegaly:
after the epiphyses close, abnormally high levels of GH result in acromegaly. This condition occurs because IGF-1, although it can no longer stimulate long bone growth, can still promote growth of organs and cartilaginous tissue.
(i) Inhibitors of GH release
Octreotide & Lanreotide (Synthetic, longer acting peptide analogues of somatostatin).
For Acromegaly
Used to control GI bleeding from esophageal varices
Antagonists of GH receptor:
- Pegvisomant
- Indications: Acromegaly & Cushing’s disease
- allow once-daily dosing
Hypothalamic-Pituitary-Prolactin Axis
- under tonic inhibition by hypothalamic release of dopamine
- interrupts the hypothalamicpituitary portal system results in decreased secretion of most anterior pituitary gland hormones but causes increased prolactin release.
- Prolactin secretion does not appear to be regulated by any identified negative feedback system.
Pharmacological agents that Inhibit pituitary prolactin release
- Bromocriptine: synthetic DA receptor agonist
- -Indications:
- Hyperprolactinemia
- Acromegaly
- Parkinson’s disease
- Diabetes mellitus type 2
- Non-pregnancy related amenorrhea-galactorrhea syndrome
- Use of bromocriptine to suppress lactation in postpartum women is not recommended.
- the area postrema in the medulla, which stimulates nausea and lies outside the blood–brain barrier, possesses dopamine receptors
agents that Inhibit pituitary prolactin release
