BIO 5406 Notes, 1/24/05
PITUITARY (Pt. 1)
I. Introduction. [Hadley, pp. 89-90]
A. Anatomy.
1. Located beneath the hypothalamus, posterior to optic chiasm.
2. Alternative name -- hypophysis.
3. Attached to hypothalamus by stalk.
4. Weighs about 1 gram in human.
B. History.
1. Early discoveries based on patients with pituitary tumors and effects
of surgical removal of the pituitary in animals -- hypophysectomy.
2. Classic experiment of Philip Smith in 1927a:
"Hypophysectomy in the rat gives an invariable syndrome, the main
features of which are: An almost complete inhibition in growth in
the young animal and a progressive loss of weight in the adult; anatrophy of the genital system with loss of libido sexualis, and in
the female an immediate cessation of the sex cycles; an atrophy
of the thyroids, parathyroids and suprarenal cortex; and a
general physical impairment characterized by a lower resistance
to operative procedures, loss of appetite, weakness and a flabbiness
that readily distinguishes the hypophysectomized from the normal
animal. It seems unlikely that they can live an average life span."
a Smith, P.E. The disabilities caused by hypophysectomy and their repair. J. Am. Med.
Assoc. 88: 158-161, 1927.
II. Divisions of the Pituitary. [pp. 90-95]
A. Posterior pituitary.
1. Embryology (fig. 5.2).
a. Derived from neuroectoderm.
b. Outgrowth of diencephalon.
2. Histology.
[Section of pituitary (very low power)b]
[Section of pituitary (low power)][Section of pituitary (low power)]
a. Nerve endings -- neurohypophysis.
b. Neuroglial cells (pituicytes).
3. Subdivisions. [Regions of the pituitary]
a. Pars nervosac.
1. Contains axonal endings of neurons originating in the
hypothalamus.
2. Secretes vasopressin and oxytocin.
b. Infundibulum (stalk).
1. Contains axons of hypothalamic neurons that terminate in
pars nervosa.
B. Anterior pituitary. [Structure of the pituitary]
1. Embryology (fig. 5.2).
a. Derived from oral ectoderm.
b. Develops from Rathke's pouch, an outgrowth of the roof of themouth.
2. Histology.
[Section of pituitary (very low power)]
[Section of pituitary (low power)][Section of pituitary (low power)]
a. Epithelial structure -- adenohypophysis.
3. Subdivisions.
a. Pars distalis.
1. Largest portion.
2. Secretes six different hormones.
3. Variety of cell types can be identified by light microscopy using
selective staining techniques. [Pituitary (medium power)]
a. Acidophils -- cytoplasmic granules bind to acidic stains.
[Pars distalis, mostly acidophils (H & E)]1. Most abundant -- 75% of cells.
2. Secrete growth hormone or prolactin.
b. Basophils -- bind to basic stains.
[Pars distalis, mostly basophils (H & E)d]1. Secrete TSH, ACTH, FSH, and LH.
c. Chromophobes -- do not take up stain.
1. May be inactive or undifferentiated cells.
b. Pars intermedia.
1. Lies between pars distalis and pars nervosa.
[Section of pituitary (low power)]2. Also known as intermediate lobe.
3. One cell type -- melanotropese.
4. Produces melanocyte-stimulating hormone (MSH).
c. Pars tuberalis.
1. Most rostral.
2. Same three cell types as pars distalis.
3. Suggests pars tuberalis is fragment of pars distalis.
b Slides are from the Texas Tech University Health Sciences Center Histology Collection.
c Slides are from The JayDoc HistoWeb, University of Kansas Medical Center Department
of Anatomy and Cell BiologyCenter.
d Slides are from the Loyola University Lumen Histology Slide Series.
e Slides are from the University of Bristol Department of Anatomy Image Library.
III. Neurohypophysis. [pp. 104, 138-142]
A. First crude preparation of mammalian pars nervosa tested in 1895.
1. Four major biological actions.
Pitocin / a. Stimulation of uterine contractions (uterotonic).
(oxytocin) <
\ b. Milk ejection.
Pitressin / c. Elevation of blood pressure (pressor).
(vasopressin) <
\ d. Reduced urine volume (antidiuretic).
B. Chemistry.
1. Structures of oxytocin and vasopressin were determined and
synthesized in the 1950's by Vincent du Vigneaud.
a. First brain peptides identified.
b. 1955 Nobel Prize in Chemistry.
2. Both mammalian neurohypophysial hormones are cyclic
nonapeptides (fig. 7.2).
a. 6-aa ring (2 cystines linked by sulfhydryl bond).
b. 3-aa side chain.
3. Oxytocin (OXY) differs from arginine-vasopressin (AVP) at positions
3 and 8 (table 7.1).a. Very little overlap in biological activity.
C. Site of biosynthesis of neurohypophysial hormones.
1. Experiments from the early 1950's.
a. Staining for neurosecretory granules show them to be present
in cell bodies in the hypothalamus and along axons extending to
pars nervosa.
b. In rats, dehydration leads to depletion of stainable material in
hypothalamic neurons.1. Suggests that the stainable material is AVP, which is released
from granules in response to dehydration.
c. Cut pituitary stalk in frogs ----> stainable material accumulates in
the tract proximal to the cut.
d. Conclusion:
D. Biosynthesis.
1. Specific hypothalamic nuclei involved in mammals (fig. 7.1).
a. OXY ----> paraventricular nucleus.
b. AVP ----> supraoptic nucleus.
2. Synthesized as prohormones (>100 a.a.).
a. Hormone (9 a.a.) + neurophysin (100 a.a.).
b. Different neurophysin for AVP and OXY.
3. Packaged into secretory granules.
a. Hormone and neurophysin cleave within granule (figure).
b. Remain loosely bound.
c. Neurophysins serve as intracellular transport proteins.
4. Secretory granules travel down axon at 3 mm/day -- axoplasmic
transport.
5. Stored in axon terminal.
E. Secretion.
1. Secretion is stimulated by an action potential.
2. Hormone and neurophysin are secreted together.
IV. Vasopressin. [pp. 149-152]
A. Antidiuretic effect.
1. Clinical observations.
a. Lesions of pituitary led to abnormally high production of dilute urine
----> diabetes insipidus.b. Administration of pars nervosa extracts reduced urine volume
and increased specific gravity.
2. Review of function of nephron.
a. Glomerular filtration (figure).
b. Reabsorption of various substances from tubule.
c. Other substances are added to tubular fluid by tubular secretion.
d. Concentration gradient of renal extracellular fluid is established by
loop of Henle.
e. If collecting duct is permeable to H2O ----> H2O is reabsorbed ---->
urine is concentrated.
f. If not, dilute urine passes through collecting duct and is excreted in
large amounts.
3. AVP permits reabsorption of water by epithelial cells of distal tubule
and collecting duct (fig. 7.15).
a. In the absence of AVP, luminal membrane is impermeable to H2O.
b. Membrane receptors on basal (blood) side of tubular cell.
c. Stimulates adenylate cyclase ----> increased cyclic AMP.
d. Inserts water channels (aquaporins) into luminal membrane
(fig. 7.14).
e. Increases permeability of the luminal membrane to water.
f. Channels are taken back up into the cell when binding of AVP is
terminated.
B. Pressor effect.
1. Pressor effect requires much higher concentrations than antidiuretic
effect.
2. Acts directly on vascular smooth muscle to cause vasoconstriction.
3. Does not involve cyclic AMP.
4. Physiological importance is complicated by the presence of various
cardiovascular reflexes.
C. Receptor subtypes.
1. Identified using vasopressin analogs.
2. V1 receptors.
a. Vascular smooth muscle.
b. Pressor effect.
c. Does not involve cyclic AMP.
3. V2 receptors.
a. Renal tubular cells.
b. Antidiuretic effect.
c. Cyclic AMP-dependent.
D. Control of AVP secretion.
1. Two controlled variables.
a. Blood pressure and volume.
1. Decrease BP ----> increase AVP secretion.
b. Plasma osmolarity.
1. Increaase plasma osmolarity ----> increase AVP secretion.
2. Example: Dehydration.
3. Effects of drugs on AVP secretion.
a. Inhibited by ethyl alcohol.
b. Stimulated by nicotine.
E. Diabetes insipidus.
1. Symptoms -- excessive urination, thirst.
2. Neurogenic diabetes insipidus.
a. Failure to secrete AVP.
b. Treatment -- replacement therapy with vasopressin analog,
desmopressin.1. Specific for V2 receptors.
2. More than 1,000x more potent than arg-vasopressin (table 7.2).
3. 3- to 5-fold longer duration of action.
4. Nasal spray.
3. Nephrogenic diabetes insipidus.
a. Failure of renal tubular cells to respond to AVP.
b. Elevated AVP levels.
F. Nocturnal enuresis (bed-wetting).
1. Usually represents a delay in maturation.
2. AVP levels normally rise at night.
a. Remain low in bed-wetters.
3. Treatment -- intranasal desmopressin at night.
V. Oxytocin. [pp. 144-149]
A. Uterotonic effect.
1. Stimulates contraction of uterine smooth muscle.
2. Mechanism.
a. OXY binds to membrane receptors.
b. Action is not mediated by cAMP.
1. Stimulates IP3 production.
c. Increased intracellular Ca++ ----> smooth muscle contraction.
d. Stimulates endometrium to produce prostaglandin F2a.
1. PGF2a stimulates contraction of uterine smooth muscle.
3. Interactions.
a. Estrogen stimulates OXY receptor synthesis.
1. Uterus becomes progressively more sensitive to OXY as pregnancy
progresses.
b. Progesterone inhibits uterine contractility.
1. Progesterone levels fall at term ----> uterus becomes more
sensitive to OXY.
c. Uterine contractions stimulate OXY secretion and PG production ---->
positive feedback loop.
4. Primary clinical use of OXY ----> induction of labor.
B. Milk ejection.
1. OXY causes contraction of myoepithelial cells in mammary glands ---->
milk ejection (fig. 7.6).
2. Does not stimulate milk production.
3. Milk ejection reflex (fig. 7.3).
a. Neuroendocrine reflex.
b. Stimulation of nipples ----> paraventricular n. ----> OXY secretion
----> contraction of myoepithelial cells ----> milk ejection.
c. Milk ejection occurs within 10-12 seconds of stimulation (fig. 7.3).
VI. Evolution of the Neurohypophysial Hormones.
[pp. 141, 152-153, 159-160]
A. Ten different neurohypophysial nonapeptide hormones (table 7.1).
B. Differences occur only in positions 3, 4, and 8.
1. Most differences can be explain by a point mutation of a single gene.
C. Evolutionary precursor -- arg-vasotocin (AVT).
1. Present in all nonmammalian vertebrates.
2. Also found in pars nervosa of fetal mammals.
3. Ring structure of OXY and the side chain of AVP.
4. Both OXY- and AVP-like effects.
a. Involved in regulation of water balance in amphibians.
b. Increases oviduct motility in reptiles and birds (fig. 7.12).
D. Primitive oxytocin -- mesotocin.
1. OXY-like in structure and activity.
2. Found along with AVT in amphibians, reptiles, and birds.
E. AVP and OXY appear for the first time in mammals.
![Regions of the pituitary]](http://ux1.eiu.edu/~klmcgilliard/fig/fox7/1112.jpg){kind=link}
