Endocrine Physiology

Dale Buchanan Hales, PhDDepartment 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 ActivityRate 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

• 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.

Episodic secretion of hormones

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