Lecture 6.1 - The Hypothalamic-pituitary axis and growth hormone

Hypothalamic Pituitary Axis

• The hypothalamic and pituitary gland forms a complex functional unit that serves as the major link between the endocrine and nervous systems
• Modulates a wide variety of processes: • Body growth • Reproduction • Adrenal gland function • Water homeostasis • Milk secretion • Lactation • Thyroid gland function • Puberty

Pituitary Gland

• Consists of two parts: • Anterior pituitary gland (adenohypophysis) - endocrine tissue • Posterior pituitary gland (neurohypophysis) - nerve tissue
• The anterior and posterior pituitary glands have distinct embryological origins and distinct functions: • Anterior pituitary arises from evagination of oral ectoderm (Rathke's pouch) - primitive gut tissue • Posterior pituitary originates from neuroectoderm - primitive brain tissue

Neurocrine Function of Posterior Pituitary

• Hormones produced in the hypothalamus
• Oxytocin and antidiuretic hormone (vasopressin) produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus
• Transported down nerve cell axons in vesicles to the posterior pituitary
• Stored and released from posterior pituitary nerve endings into the general circulation to act on distant targets

Anterior Pituitary Function

• Hormones synthesized in the hypothalamus are transported down axons and stored in the median eminence before release into the hypophyseal portal system
• These hormones stimulate (or inhibit) target endocrine cells in the anterior pituitary gland (neurocrine function)
• Endocrine cells of the anterior pituitary secrete a variety of hormones into the bloodstream to act on distant target cells (endocrine function)

Tropic Hormones of the Hypothalamus

• 6 tropic hormones (stimulating) produced in the hypothalamus: • TRH (thyrotropin-releasing hormone) • PRH (prolactin-releasing hormone) = TRH (minor +ve control on prolactin) • PIH (prolactin-release-inhibiting hormone) (dopamine) • CRH (corticotropin-releasing hormone) • GnRH (gonadotropin-releasing hormone) • GHRH (growth hormone-releasing hormone) • GHIH (growth hormone-inhibiting hormone) (Somatostatin)

Hormones Produced by the Anterior Pituitary

• TSH (thyroid-stimulating hormone)
• ACTH (adrenocorticotropic hormone)
• LH (luteinizing hormone)
• PRL (prolactin)
• GH (growth hormone)

Negative Feedback

• The pathways by which hypothalamic and anterior pituitary hormones are produced are often regulated by negative feedback: • Short loop or long loop negative feedback pathways

Growth Hormone

• Produced in the anterior pituitary: • Stimulated by hypothalamic GHRH • Inhibited by hypothalamic somatostatin
• Protein hormone (191 aa) has signal peptide that must be cleaved before proper folding
• Growth-promoting effects mainly exerted indirectly via insulin-like growth factors (somatomedins)

Control of GH Secretion

• Principle control is via the hypothalamus: • GHRH -> increases GH secretion • Somatostatin -> decreases GH secretion
• CNS regulates GH secretion via inputs into the hypothalamus effecting GHRH and somatostatin
• GH secretion is regulated by long loop and short loop negative feedback

Growth Hormone Deficiency

• In childhood, results in pituitary dwarfism
• Proportionate type of dwarfism
• Complete or partial deficiency
• Both types respond to GH therapy

Growth Hormone Excess

• In childhood, results in GIANTISM
• In adulthood, leads to acromegaly: • Characterized by large extremities: • Hands • Feet • Lower jaw

Insulin-Like Growth Factors (IGFs)

• 2 IGFs in mammals (IGF1 and IGF2)
• Binding proteins modulate their availability in the blood
• Actions of IGFs can be paracrine and autocrine as well as endocrine
• IGFs act through IGF receptors (distinct from GH receptors) to modulate: • Cell growth (hypertrophy) • Cell number (hyperplasia) • Increase in the rate of protein synthesis • Increase in the rate of lipolysis in adipose tissue