Transcript Endocrine Physiology - bushelman-hap

Endocrine Physiology
Dale Buchanan Hales, PhD
Department of Physiology & Biophysics
Regulation of hormone
secretion
 Sensing and signaling: a biological need is sensed,
the endocrine system sends out a signal to a target
cell whose action addresses the biological need.
Key features of this stimulus response system are:





receipt of stimulus
synthesis and secretion of hormone
delivery of hormone to target cell
evoking target cell response
degradation of hormone
Control of Endocrine Activity
•The physiologic effects of hormones depend
largely on their concentration in blood and
extracellular fluid.
•Almost inevitably, disease results when hormone
concentrations are either too high or too low, and
precise control over circulating concentrations of
hormones is therefore crucial.
Control of Endocrine Activity
The concentration of hormone as seen by target
cells is determined by three factors:
•Rate of production
•Rate of delivery
•Rate of degradation and elimination
Control of Endocrine Activity
Rate of production: Synthesis and secretion of
hormones are the most highly regulated aspect of
endocrine control. Such control is mediated by
positive and negative feedback circuits, as described
below in more detail.
Control of Endocrine Activity
Rate of delivery: An example of this effect is
blood flow to a target organ or group of target
cells - high blood flow delivers more hormone
than low blood flow.
Control of Endocrine Activity
Rate of degradation and elimination: Hormones,
like all biomolecules, have characteristic rates of
decay, and are metabolized and excreted from the
body through several routes.
Shutting off secretion of a hormone that has a very
short half-life causes circulating hormone
concentration to plummet, but if a hormone's
biological half-life is long, effective concentrations
persist for some time after secretion ceases.
Feedback Control of Hormone
Production
Feedback loops are used
extensively to regulate
secretion of hormones in the
hypothalamic-pituitary axis.
An important example of a
negative feedback loop is seen
in control of thyroid hormone
secretion
Inputs to endocrine cells
Neural control
• Neural input to hypothalamus stimulates
synthesis and secretion of releasing factors
which stimulate pituitary hormone
production and release
Hormonal control
• Hypothalamus regulates anterior pituitary
hormone production and release.
• Hormones from anterior pituitary glands
stimulate other glands in endocrine system
to release hormones.
Chronotropic control
• Endogenous neuronal rhythmicity
• Diurnal rhythms, circadian rhythms (growth
hormone and cortisol), Sleep-wake cycle;
seasonal rhythm
Episodic secretion of
hormones
• Response-stimulus coupling enables the
endocrine system to remain responsive to
physiological demands
• Secretory episodes occur with different
periodicity
• Pulses can be as frequent as every 5-10
minutes
Episodic secretion of hormones
• The most prominent episodes of release occur
with a frequency of about one hour—referred to as
circhoral
• An episode of release longer than an hour, but less
than 24 hours, the rhythm is referred to as
ultradian
• If the periodicity is approximately 24 hours, the
rhythm is referred to as circadian
– usually referred to as diurnal because the increase in
secretory activity happens at a defined period of the
day.
Circadian (chronotropic) control
Circadian Clock
Physiological importance of
pulsatile hormone release
• Demonstrated by GnRH infusion
• If given once hourly, gonadotropin secretion and
gonadal function are maintained normally
• A slower frequency won’t maintain gonad
function
• Faster, or continuous infusion inhibits
gonadotropin secretion and blocks gonadal steroid
production
Clinical correlate
• Long-acting GnRH analogs (such as
leuproline) have been applied to the
treatment of precocious puberty, to
manipulate reproductive cycles (used in
IVF), for the treatment of endometriosis,
PCOS, uterine leiomyoma etc
Feedback control
• Negative feedback is most common: for example,
LH from pituitary stimulates the testis to produce
testosterone which in turn feeds back and inhibits
LH secretion
• Positive feedback is less common: examples
include LH stimulation of estrogen which
stimulates LH surge at ovulation
Negative feedback effects of cortisol
Nonhormonal control
• Glucose and insulin: as glucose increases it
stimulates the pancreas to secrete insulin
Feedback control of insulin by
glucose concentrations