Lecture Outline #7:  The Endocrine Hypothalamus

 

I.  INTRODUCTORY REMARKS

1.  The hypothalamus (hypothalamus) is a neuroendocrine area which acts as a "transducer" to convert neuronal activity into hormonal secretions. (Fig. A) (Fig. 5.3)  (For additional information, click.)

2.  It is like the "head ganglion" of the autonomic nervous system.

3.  It is especially concerned with cardiovascular, respiratory, GI, and reproductive control.

4.  It exhibits pulsatile, circadian (circadian), and sex cycle rhythms in its secretion.

5.  It is associated with emotions such as fear, rage, aversion, pleasure, and reward:

(a)  stimulation of certain areas of the hypothalamus in experimental animals causes hissing, growling, clawing, showing of fangs, piloerection, arching of the back, and striking out, and

(b)  stimulation of "reward" areas gives pleasure (leading to repeated self-stimulation in experimental animals).

 

II.  ANATOMY OF THE HYPOTHALAMUS

1.  Terminology of the central nervous system:

(a)  nuclei are zones of histologically distinct groups of cells in the CNS

(b)  areas are zones with experimentally definable functions, but these zones are not distinguishable as anatomical entities

(c)  tracts are “nerves” in the CNS--consisting of groups of unmyelinated nerve axons.

2.  Hypothalamic input:

(a)  it has direct or indirect neural contact with virtually every area of the brain

(b)  it is connected to cerebrospinal fluid by large cuboidal epithelial cells called tanycytes that line the floor of the 3rd ventricle

(c)  it connects with the blood, i.e., the systemic circulation.

3. Hypothalamic output: (this output is by neurosecretory cells that make up two major tracts  (Fig. 5.4)

(a)  the tuberoinfundibular tract starts with parvicellular neurons made of small, less defined cell bodies in the arcuate nuclei and the hypophysiotropic area, and their axons travel to the vicinity of the median eminence within the primary capillary plexus of the superior hypophysial artery (hypophysial) (which forms a capillary bed that picks up hypothalamic secretions and carries them into the hypothalamo-hypophyseal portal vessels to the adenohypophysis.

(b)  the hypothalamohypophysial tract starts with magnocellular neurons that are larger cells located in the supraoptic (supraoptic) and paraventricular nuclei, and their axons travel through the infundibulum to the posterior pituitary.  (Fig. 5.5)  (Fig. 6.1)  (Fig. 6.1.A)

4.  Properties of the neurosecretory cells of the hypothalamus: (Fig. B)

(a)  They (1) receive and process stimuli from all parts of the CNS, (2) conduct action potentials along their axons, and (3) synthesize and release hormones into the circulatory system.

(b)  More specifically, they produce peptide prohormones by mRNA on ribosomes in their nerve cell bodies, and then convert these prohormones to active hormones during the process of axoplasmic transport along axon filaments.

(c  They store the hormones in vesicular granules at their axon terminals until depolarization of the plasma membrane causes exocytosis (exocytosis).

 

III.  RELEASING HORMONES KNOWN TO REGULATE PITUITARY SECRETIONS

 

A.  SOMATOTROPIN REGULATION

1.  Somatotropin (SH) stimulates mitosis of connective tissues and IGF secretion by the liver.

2.  ­ GHRH (or, somatocrinin) is a 44 AA peptide isolated by Guillemin.  (and ­ by ghrelin)

3.  ¯ Somatostatin (or, SRIF) is a 14-28 AA peptide that inhibit both STH and PRL secretion.

4.  Somatostatin also inhibits release of TSH, as well as many GI hormones and pancreatic hormones.

B.  PROLACTIN REGULATION

1.  Prolactin (PRL) promotes lactation in mammary tissue, and suppresses sex hormone secretion.

2.  ­ TRH, VIP and oxytocin increase PRL secretion, but no specific releasing hormone yet found.

3.  ¯ Dopamine from the arcuate nuclei is the chief inhibitor of PRL release.

4.  Dopamine also appears to have a major role in rewarding sensations following food or sex.

 

C.  THYROTROPIN REGULATION

1.  Thyrotropin (TSH) stimulates the thyroid gland to produce T4 and T3.

2.  ­ TRH is well known as the principal inducer of TSH secretion (Guillemin & Schally).

3.  ¯ Somatostatin appears to be the most significant inhibitor of TSH secretion.

4.  TSH is the specific hormone that is measured to determine hypothyroidism and hyperthyroidism.

D.  GONADOTROPIN REGULATION  (GnRH)

1.  Gonadotropins are hormones such as FSH, LH and hCG that stimulate the gonads.

2.  ­ GnRH stimulates FSH & LH.  (so does dopamine)

3.  ¯ Met-enkephalin inhibits dopamine and, thus, indirectly inhibits GnRH.

4.  Like most releasing hormones, GnRH must be secreted in a pulsating rhythm to be effective.

(5.  GnRH is also affected by nor-epinephrine, GABA, glutamate, AgII, NP-Y, 5-HT, Il-1, etc.)

 

E.  CORTICOTROPIN REGULATION

1.  Actually, this is POMC regulation, since corticotrophin is a derivative of POMC.

2.  ­ CRH is the principal releasing hormone, but catecholamines also induce CRH release.

3.  ¯ There is no distinct inhibitor of POMC and ACTH, but maybe acetylcholine.

4.  Keep in mind that the more stress, the more POMC and ACTH secretion.

 

IV.  A REVIEW OF “FEEDBACK CONTROL” OF PITUITARY HORMONE SECRETION

            Keep in mind that, with the exception of prolactin, secretion of most adenohypophyseal hormones is regulated to a large extent by the hormones they stimulate in systemic glands.  (Fig. 6.16)

V.  MECHANISM OF ACTION OF RELEASING HORMONES

            Briefly, it is important to note that the hypothalamic releasing hormones described in the previous section act on their respective target cells in the adenohypophysis by coupling with plasma membrane receptors and causing ion gating that elicits action potentials in the target cells.  (Fig. 6.19)

V.  THE NEUROHYPOPHYSEAL EXTENSION OF THE HYPOTHALAMUS  (Fig. 5.5)

1.  40% of the neurohypophysis is neuronal tissue (mainly axons and axonal endings) from the magnocellular neurons of the SO & PV nuclei.

2.  60% of the neurohypophysis is supporting tissue known as pituicytes (or, neuroglial cells) which might also be the source of neurophysins, which are large carrier proteins for the two neurohypophyseal hormones described below.

A.  OXYTOCIN (PIT)

1.  Oxytocin is a nonapeptide secreted as the result of a reflex arc from the nipples or uterus.

2.  It is produced in cells of the paraventricular nuclei in association with neurophysin I, a carrier protein that facilitates the movement of oxytocin along the axon of the neurosecretory cell.

3.  Once secreted, it stimulates mammary and uterine smooth muscle contractions by binding to specific GPCRs, elevating cytosolic Ca++ in the smooth muscle cells.

B.  ARGININE VASOPRESSIN  (antidiuretic hormone (antidiuretic hormone), or ADH)

1.  The other neurohypophyseal hormone is highly homologous to oxytocin, but it is secreted when hypertonic plasma (i.e., blood plasma that is too concentrated) stimulates action potentials in osmotically sensitive magnocellular neurons.

2.  Vasopressin is produced in neurohypophyseal cells in association with neurophysin II.

3.  Once secreted, it promotes:

a.  the collecting ducts and distal tubules in the renal nephrons to reabsorb water.

b.  the constriction of peripheral blood vessels and increases blood pressure.

c.  it also might support retention of conditioned reflexes and memory???

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