Endocrinology I

Introduction

I. Intercellular Communications: Different ways to communicate between cells such as chemically or electrically – Different sorts of molecules communicate different ways

A. Paracrines: Compounds that affect an adjacent cell

1. They don’t get into the circulatory system

2. Chemical diffuses to its neighbor
B. Neurotransmitters: Really don’t get into the circulation but diffuse from presynaptic neuron to postsynaptic neuron

1. The neuron is where it is synthesized

2. Really a paracrine but specialized so called this instead

C. Hormones: Specialized molecules that are produced by the endocrine cell in response to a stimulus

1. Carried to the target by the circulatory system

2. Target has receptors on it that recognize the hormones
D. Neurohormones: Neuron or neuronal tissue secrete these into the circulatory system to some target far away

E. Autocrine Secretions: Produced by a cell and has an affect on the cell that secreted it

***If we compare the Endocrine System with the Nervous System: The nervous system is hard wired with neurons and works electrically via an action potential and neurotransmitters cell to cell; It involves rapid transmission and the response is short lived – The endocrine system works via chemical communicators (hormones) which travel long distances (comparatively); There is a slower response time but it is long lived

II. Feedback Mechanisms

A. Simple: Do not require hormonal feedback

1. Non hormonal feedback: Endocrine cells release hormone to target which has a response and returns the message

2. EX: Glucose and Insulin regulation: Increased plasma glucose causes insulin to be secreted which makes plasma glucose levels decrease and the insulin secretions decrease and so on

B. Complex (multilevel): Involve hormonal feedback

1. The hypothalamus releases TRH which stimulates the anterior pituitary gland to release TSH which goes to the thyroid gland to release T4 and T3 which results in a biological response

2. Hormones will come back to inhibit the hypothalamus, the anterior pituitary and the thyroid to shut off the system

III. Chemical Nature of Hormones: Affects a lot of characteristics

A. Amino Acid Derivatives: Formed by the simple conversion of common amino acids – EX: Epinephrine and thyroxin
B. Peptide and Protein Hormones: Larger peptides and larger protein hormones
C. Steroids: Lipid soluble, hydrophobic, and lypophilic – Synthesized from cholesterol

1. All hormones are transported by the blood so if something is hydrophobic then you have to attach a plasma protein to it to get it transported

IV. Synthesis

A. Peptide and Protein: Synthesized within the cell in the ribosomes – Ribosome makes the prohormone (not quite a hormone) and the hormone is taken up into the Golgi apparatus to make the right hormone molecule and then stored in the cell

1. When it is appropriate the cell is stimulated to exocytose the hormone to the plasma

B. Steroid: Made from cholesterol within the cell but they are not typically stored

1. They are released on the appropriate signal

2. Steroids pass right through the membrane

3. Steroids are mostly found in the nucleus

V. Mechanism of Action

A. Proteins

1. 2nd. Messenger: If proteins cannot get through the membranes then they use a second messenger of some time
2. Change in Membrane Permeability: Some proteins change the permeability of the membrane

B. Steroids: Pass right through the membrane

***Cycles of hormones aren’t necessarily concrete, some things supercede and intervene in the above models – Some things complicate the system like a single endocrine gland produces more than one hormone and a single hormone is produced by more than one gland and targets are influenced by more than one hormone, etc.,

Hypothalamus - Pituitary
and the
Pineal Gland

I. Introduction: These two structures from the most complex and the most dominant portion of the endocrine system – Sometimes elaborate and sometimes subtle – Responsible for the functions of the thyroid, adrenal, and the reproductive glands, etc., - Despite all of this the entire structure only weighs 500 mg (Hypothalamus) and 10 mg (Pituitary gland) and there isn’t a lot of tissue – The pituitary gland or the hypophysis is located at the base of the brain and is protected by the sphenoid bone (a satellite depression on the sphenoid bone called the sella turcica) – The pituitary gland sits right down in it and is a vital gland – Every time doctors/scientists tried to remove it the animal died but this is not true anymore because it was the surgery that killed the animals not the loss of the pituitary – Reason died was because it is so well protected at the sella turcica – The hypophyss is closely associated with the hypothalamus and are connected by a stalk like structure – The pituitary gland is divided into two separate portions (2 parts of same gland) which are very different and have different embryological origins

A. Anterior Pituitary – Adenohypophyss: Synonym for anterior pituitary
B. Posterior Pituitary – Neurohypophysis: Connected to the hypothalamus

II. Embryology

A. Anterior Pituitary: Derived from Rathke’s Pouch which is off of the digestive system of a developing embryo

B. Posterior Pituitary: In the developing brain of the embryo, the infundibulum gives rise to the posterior pituitary

1. Rathke’s pouch breaks off and migrates up to the infundibulum until it is a part of it

III. Adult Anatomy: Rathke’s pouch surrounds the infundibulum until an adult

A. General Anatomy - See Fig. 1
B. Ant. Pituitary Cell Types and Hormones Secreted: Within the anterior pituitary find several different cell types and they each make different hormones

1. Somatotroph: Makes Human growth hormone (HGH) and is the mose prevalent of cells
2. Lactotrophs: Makes Prolactin
3. Coricotroph: Makes Adrenalcorticotrophic hormone (ACTH) and Melanocyte stimulating hormone (MSH): MSH is important in some species but not in humans – These two hormones are very similar to each other and if humans are exposed to MSH then they have a response as if they were exposed to ACTH
4. Thyrotroph: Makes Thyroid stimulating hormone (TSH) and is not prevalent

5. Gonadotroph: Makes Follicle stimulating hormone (FSH) and Luteinizing hormone (LH)

6. Most of these only make one hormone but some make more than one – Hormones of the anterior pituitary are derived from Rathke’s Pouch

IV. Anatomical and Physiological Relationships between the Hypothalamus and Pituitary

A. Neural relationships and posterior pituitary

1. The infundibular stalk contains bundles of nerve fibers which originate in the hypothalamus and end in the posterior pituitary next to the capillary bed – These tracts are from 2 origins:

a. From the supra optic nucleus: Produce predominantly ADH

b. From the paraventricular nucleus: Produce predominantly oxytocin hormones (ADH or oxytocin) and are made in the nucleus of the hypothalamus and are transmitted through the neuron (axon) – Carries hormones down to the end of the neurons and wait for release (next to capillary bed) – Just stored and released at the posterior pituitary

B. Circulatory relationships - anterior pituitary - hypophyseal portal system and releasing/inhibiting hormones: Not a neuronal relationship but a vascular relationship – Arterial flow comes in to the capillary bed and the artery (hypophyseal portal vein) to the second capillary bed to the venous outflow (superior hypophyseal artery comes in) – The first capillary in the hypophyseal and the second artery is in the anterior pituitary – Cells in the anterior pituitary produce there own hormones and the hormone’s activity is regulated by releasing or inhibiting factors (hormones) which are made by neurons in the hypothalamus – They’re released to the capillary bed and go down to the anterior pituitary to regulate the anterior pituitary hormones – Signals from the anterior pituitary go up to the hypothalamus to cause the release of the regulating hormones and then go down to regulate the release of anterior pituitary hormones

1. Thyrotropin releasing hormone (TRH): Stimulates the release of TSH and Prolactin
2. Corticotropin releasing hormone (CRH): Stimulates the release of ACTH and MSH
3. Gonadotropin releasing hormone (G_nRH): Stimulates the release of FSH and LH
4. Growth hormone releasing hormone (GHRH): Stimulates the release of HGH
5. Growth hormone inhibiting hormone (GHIH or somatostatin): Inhibits the release of HGH
6. Prolactin inhibiting hormone (PIH): Inhibits the release of prolactin (probably dopamine)

V. Anterior Pituitary Hormone Functional Overview

A. F.S.H.: Follicle stimulating hormone

1. Growth and maturation of the ovarian follicles

2. Influences estrogen secretion from the follicle

3. Stimulates sperm production
B. L.H.: Luteinizing Hormone

1. A surge of LH is needed for ovulation

2. Formation of the corpus luteum (follicle reorganized and forms corpus luteum)

3. Secretion of testosterone by the Leydig cells
C. A.C.T.H.: Adrenocorticotropic hormone

1. Stimulates the production of the glucocorticoids by the adrenal cortex (adrenal gland) – A hormone like cortisoid

D. T.S.H.: Thyroid stimulating hormone

1. Growth/maintenance of the thyroid tissue and stimulates the secretion of the thyroid hormone

E. Prolactin: Causes milk production and secretion of milk in the mammary glands

1. Secretion: There are alveolar sacs lined with secretory epithelial cells (synthesize milk) – Prolactin causes the secretion of the milk into the sacs

F. H.G.H.: Human growth hormone

1. Role in body growth and the regulation of metabolism

G. Melanocyte stimulating hormone (MSH): Associated with the intermediate lob (in adults) – In animals MSH is produced

1. No significant role in humans

2. Role in camouflage in some animals – Affects the distribution of pigments – If pigment is distributed throughout the cell it takes on a darker color so animals have a darker color than humans

3. ACTH influence: Can influence of the hue of color in humans

VI. Intermediate Lobe Hormone Functional Overview

A. ADH: Also called Vasopressin

1. Produced by the supra optic nucleus and transmitted down the neurons and has a role in urine production and regulating blood pressure

B. Oxytocin

1. Produced by the paraventricular nucleus and stimulates milk let down and may play a role in parturition

2. Milk led down: Milk is secreted to the alveolar sac but it has to go through a ductile system to the nipple where it can be suckled – The cells right under the sac are myoepithelial cells that have oxytocin receptors on them which cause them to contract so the milk is let down to the nipple – Oxytocin is caused to be released by sucking of the infant at the nipple (a neuroendocrine reflex: neuro at the afferent side and endocrine at the efferent side) – Suckling impulses to the maternal brain, integrating circuit, causes oxytocin I the posterior pituitary to be released and lets milk down to the nipple – This reflex can be easily conditioned and other stimuli can cause milk let down – Unconditioned would be the stimulus from suckling but conditioned is like hearing the baby cry

3. Oxytocin is a partner to parturition: Oxytocin can stimulate the uterus (myometrium) and cause parturition (induce labor by Pitocin – synthetic oxytocin) – Oxytocin levels increase after parturition has already begun (EXP: Remove the posterior pituitary in rats but they still parturate on the right day it just takes longer)

4. Oxytocin has also been implicated in assisting sperm transport – Sperm go from the vagina to the oviduct in less time than just swimming could take (just few minutes) – Sex causes oxytocin release and increases the motility of the uterus for oxytocin travel

VII. Posterior Pit. Functional Overview

A. A.D.H.
B. Oxytocin

VIII. Pineal Gland: Not a part of the pituitary gland and is posterior to the thalamus

A. At one time it was thought to have had no known function in humans but it secretes melatonin (hormone)

1. Melatonin goes through large secretions at night and a little bit during the day and is secreted due to light

B. Pineal gland though to cause third eye or pineal eye – Located close to the optic nerve tracts which cross in the cerebrum

C. Melatonin is involved in certain functions of cyclic activity like the biological clock (day and night and jet lag, etc.,), helpful in treating effective disorders (depression is seasonal), treats PMS, puberty onset (How does the body know when to become sexually mature?), and seasonal breeding (animals)