unit 5, lesson 2, Hypothalamic-Pituitary Axis

• The lecture focuses on the Hypothalamic-Pituitary Axis, Hypothalamus, Pituitary, Hypothalamic releasing hormones, Anterior pituitary hormones, and Posterior pituitary hormones

Hypothalamic-Pituitary Axis

• This axis is a critical link between the brain and the endocrine system
• It enables the brain to impact bodily functions and is essential for maintaining homeostasis

Hypothalamus

• This is the diencephalon region of the brain, located at the base, forming the floor and sides of the third ventricle
• It lacks an effective blood-brain barrier
• It contains groups of neurons that secrete hormones and neurotransmitters
• Some hormones affect the release of trophic hormones by the anterior pituitary
• Some hormones transported down axons to be released by the posterior pituitary
• Vital for controlling food/drink intake, sexual behavior, sleep-wake cycle, blood pressure, heart rate, body temperature, and emotions

Pituitary Gland

• It is a pea-sized gland with two sub-glands: anterior and posterior, separate developmentally and anatomically
• The anterior pituitary forms from the roof of the embryonic mouth
• The posterior pituitary comes from the brain
• The anterior lobe connects to the hypothalamus via portal blood vessels in the median eminence
• The posterior lobe connects via nerves descending from the hypothalamus in the median eminence

Anterior Pituitary Hormones

• Glycoprotein hormones include follicle stimulating hormone (FSH) and luteinizing hormone (LH), both gonadotrophins and thyroid stimulating hormone (TSH), a thyrotrophin
• Somatotrophic hormones include growth hormone (GH), a somatotrophin and prolactin (PRL)
• Pro-opiomelanocortin-derived hormones include adrenocorticotrophic hormone (ACTH), a corticotrophin

Posterior Pituitary & Hypothalamus Hormones

• Posterior pituitary hormones include: Vasopressin/Arginine Vasopressin (AVP)/ Supraoptic nucleus (SON) Antidiuretic Hormone (ADH), and Oxytocin (PVN).
• Hypothalamus hormones include: Gonadotrophin Releasing Hormone (GnRH)/Luteinizing Hormone Releasing Hormone (LHRH), Thyrotrophin Releasing Hormone (TRH), Growth Hormone Releasing Hormone (GHRH), Somatotrophin release inhibiting factor (SRIF)/somatostatin, Dopamine and Corticotrophin Releasing Hormone (CRH)/Corticotrophin Releasing Factor (CRF)

Hypothalamus & Pituitary Summary

• Hypothalamus hormones include: GnRH, CRH, TRH, GHRH, somatostatin, TRH/oxytocin, and dopamine.
• Pituitary hormones include: FSH/LH, ACTH, TSH, GH, PRL.

Properties of Hypothalamic Releasing Hormones

• Release is pulsatile
• They are made by neurons, delivered by the vasculature
• They act on specific receptors on target cells in the anterior pituitary
• They stimulate or inhibit trophin synthesis/release
• Release is regulated by negative feedback

Growth Hormone Releasing Hormone (GHRH)

• GHRH stimulates the synthesis and release of Growth Hormone (GH) by specific receptors in the somatotrophs
• GHRH is a 44 amino acid peptide; the N-terminal 29 amino acids are necessary for biological action
• GHRH is related to glucagon
• GHRH is also found in the pancreas and upper intestine, but the physiological role is unknown

Somatotrophin Release-Inhibiting Factor/Somatostatin

• Somatostatin is a cyclic 14 amino acid peptide, also a 28 amino acid peptide
• It causes Receptor-mediated inhibition of the action of GHRH on somatotrophs, inhibiting secretion of TSH and prolactin by the pituitary
• Found in many other areas of the brain and body, including the GI tract and pancreas
• It suppresses the release of glucagon

Anterior & Posterior Pituitary Hormones

• LH, FSH, and prolactin are released by the anterior pitutiary
• ACTH and TRH are also released by the anterior pituitary
• Growth Hormone is also released by the anterior pituitary
• Oxytocin and Vasopressin are released by the posterior pituitary

Anterior Pituitary Hormone Targets

• TSH acts on the thyroid gland to create thyroid hormones
• ACTH acts on the adrenal gland to create corticosteroids
• FSH and LH act on the testes to make testosterone and the ovaries and to make oestrogen,
• Prolactin acts on the mamary gland
• GH acts on muscle, bone, adipose tissue
• Release hormones feedback to the hypothalamus

Growth Hormone

• It is the most abundant anterior pituitary hormone, a 191 amino acid peptide
• Somatotropes make up 50% of secreting cells
• Secretion is pulsatile, peaks twice in a cycle, rises during the first hour of sleep and is highest at night
• Levels are highest during early childhood and puberty, also essential for gonad development, but declines into adulthood
• There are interactions with other hormones such as glucocorticoids that promote production of proteins involved in effects of GH

GH Release

• GHRH stimulates GH release, while somatostatin inhibits it
• GH and IGF-1 also causes negative feedback to the anterior pituitary
• Hypoglycemia, sleep, exercise, amino acids, drugs and stress promote it
• Insulin-like Growth Factor-1 (IGF-1) causes direct negative feedback on pituitary somtotrophs
• IGF-1 stimulates somatostatin synthesis and secretion from the hypothalamus
• GH may also stimulate somatostatin secretion, and inhibit GH release

Action of Growth Hormone

• Linear growth of bone via cartilage
• Overall growth of visceral organs, adipose and connective tissue, endocrine glands and skeletal muscle
• It opposes the actions of insulin
• Acts on adipocytes to increase lipolysis (free fatty acids) and skeletal muscle to increase glucose production
• It decreases glucose uptake by tissues

Indirect Effects of GH

• It is mediated by insulin-like growth factors (IGFs), specifically IGF-1
• GH stimulates synthesis and release of IGF-1 from the liver, bone, fibroblasts, adipocytes, pituitary, and kidney
• IGFs circulate tightly bound to plasma proteins to protect them from proteolysis and bind to IGF receptors
• Bind to IGF receptors (skeletal muscle, liver adipose tissue, chondrocytes in cartilage)
• Increase protein production and cell proliferation
• Levels rise during postnatal development

IGF-1 Action

• Bone; causes proliferation and bone growth
• Skeletal muscle: causes differentiation and proliferation of myoblasts - muscle growth
• Adipose tissue: lipolysis
• Liver: Increases glucose production and protein synthesis

Vasopressin/Antidiuretic Hormone

• Its a 9 amino acid peptide made by the supraoptic nucleus and released from the posterior pituitary into the blood stream
• Regulates body fluid volume
• Causes the re-absorption of water from the distal convoluted tubules and collecting ducts, urine volume and body fluid
• Prevents diuresis or fluid loss involving V2 receptors, and has a vasoconstrictor effect

Vasopressin Release Control

• Plasma osmolarity (osmoreceptors) and blood volume/arterial pressure (baroreceptors) controls vasopressin release
• Release is increased by pain, fear, nausea, drugs, general anaesthesia and neurotransmitters, and inhibited by alcohol

Summary

• The hypothalamic-pituitary axis connects the brain to the endocrine system
• The hypothalamus releases hormones into the pituitary portal blood stream, including GHRH and somatostatin
• The anterior pituitary circulates hormones from secretory cells: and GH is essential for normal growth
• The posterior pituitary releases hormones from the hypothalamic neurons
• Vasopressin release is regulated by plasma osmolarity, essential for regulation of body fluid volume