02 - Hypothalamus-Pituitary Axis (HPA)

hypothalamus-pituitary axis (HPA)

integration bridges nervous and endocrine systems for whole-body coordination

• hypothalamus → part of brain that receives input from nervous system

• pituitary gland → responds to hypothalamic signals by secreting hormones that act on other endocrine organs

hypothalamus connection to anterior and posterior pituitary

• anterior pituitary → hypothalamo-hypophyseal portal system

  • hormones secreted by hypothalamus trav+el a short distance to stimulate pituitary for release of tropic hormones

• posterior pituitary → neural connection (neurohypophysis)

  • hormones synthesized in hypothalamus and directly transported down axons

posterior pituitary

• neural connection mainly from supraoptic nuclei in hypothalamus to posterior pituitary

• hormones release from “nerve” terminals

• hormones synthesized in supraoptic nuclei, released from posterior pituitary

  • transport involves neurophysins also produced in hypothalamus

anterior pituitary

• portal circulation 

  • hypothalamus synthesizes hypothalamic releassing hormones in paraventricular nucleus

  • pituitary releases tropic hormones

• integration

• localized circulation maintains pulsatile timing due to limited volume and single pass

peptide hormone secretion

stored in membrane granules

• released by exocytosis with Ca²⁺ influx

• degraded by liver and kidney

hormone groups of anterior pituitary

• glycoproteins → FSH, LH, TSHH, hCG

  • alpha units produced in excess, with unique beta units for specificity

  • rate-limiting production

• somatomammotropin → GH, PRL, hCS

  • growth promoting

• adenocorticotropin → ACTH, ⍺,β-MSH, LPH, β-endorphin

  • arise from same pro-hormone, pro-opiomelanocortin (POMC)

  • found in anterior, intermediate, and posterior lobes

glycoprotein hormones of anterior pituitary

all share common alpha chain but have unique residues in beta chains (rate-limiting for synthesis)

• follicle stimulating hormone (FSH)

• luteinizing hormone (LH)

• thyroid hormone (TSH)

• placental human chorionic gonadotropin (hCG)

endocrine disorders

multiple controls on hormone secretion

• primary → endocrine gland

• secondary → pituitary gland

• tertiary → hypothalamus

negative feedback peripheral

secondary from peripheral target tissue feedback, where modulation of secretion is determined by hypothalamic control

• peripheral target organs limit stimulation of pituitary by hypothalamus

• feedback occurs both at hypothalamus and directly on pituitary

• negative feedback is usually long-loop feedback

• may be short-loop feedback of hormone on pituitary

• EXCEPTION — prolactin is subject to little peripheral feedback

  • open loop control

  • may be affected by other hormones, such as estrogen

anterior pituitary regulation

primarily from CNS and secretory control from hypothalamic releasing factors

• tonic effects of hypothalamus on pituitary 

• allows for integration of both internal and external environment → feedforward regulation

• often provides information for a set-point, maintained by peripheral factors

• often release of hypothalamic factors occurring in bursts

• affect synthesis and secretion of pituitary hormones

• secondary messengers may be cAMP or phosphatidylinositol (PI) turnover to increase Ca²⁺ for hormone release

hypothalamic factors controlling anterior pituitary

• gonadotropin releasing hormone (GRH) → stimulates FSH and LH release

• thyrotropin releasing hormone (TRH) → stimulates TSH release

  • effect modulated by thyroid hormone

  • stimulates PRL release

• corticotropin releasing hormone (CRH) → stimulates ACTH, β-LPH, and β-endorphin

• growth hormone inhibitory hormone (GHIH, somatostatin) → inhibits GH release

  • may inhibit TSH release

• prolactin inhibitory hormone (PIH) and dopamine → inhibits PRL release, which is tonically active

  • major factor responsible for PRL release

other influences on secretion/synthesis

other hormones may affect control

• pattern of secretion varies with time

• none of pituitary hormones are subject to constant release

• often diurnal patterns, may be light/dark or day/night

  • often secondary to hypothalamic factors

  • pattern is not sinusoidal release but consists of multiple spiking patterns

  • mean rhythm may be generated altering frequency of burst activity