Endocrine Histology

Question 1

Introduction to Endocrine System

Answer 1

a. Many cells produce molecules that stimulate or regulate other cells.
i. Certain of these molecules are referred to as hormones, a broad class of molecules effective at low concentration that stimulate other cells via receptors.

b. Hormones that are transported in the blood to reach target cells are called endocrines.
c. Endocrine organs or glands are organs that are comprised largely of hormone-producing or -containing cells that have a rich blood supply.

Question 2

Introduction to Endocrine Organs

Answer 2

a. Endocrine organs or glands are organs that are comprised largely of hormone-producing or -containing cells that have a rich blood supply.
b. Some, such as the corpus luteum and portions of the placenta become highly elaborated under defined physiological states (i.e.—pregnancy).
c. Other organs such as the testis, pancreas and ovaries contain clusters of endocrine cells normally and still other tissues, such as the GI tract and the lung contain more diffuse scatterings of endocrine cells, some of which act locally.

d. Also associated with the autonomic nervous system are paraganglia that elaborate a variety of peptide hormones.
i. The brain has many receptors and produces many endocrine molecules.

e. Thus, the major endocrine organs constitute only a portion of the intercellular communication that occurs via blood-borne hormones.

Question 3

The Pituitary Gland

Overview

Answer 3

a. The pituitary is really two separate glands of dual origin in the shape of one organ.

b. The gland is positioned in the sella turcica at the base of the skull, the pituitary is comprised of:
1. The anterior pituitary, or adenohypophysis, made up of the pars distalis, pars intermedia, and pars tuberalis.
2. The posterior pituitary, or pars nervosa (or infundibular process), the infundibular stem or stalk, and the median eminence.

c. The anterior pituitary is derived embryonically from an outgrowth of endoderm called Rathke’s pouch, while the posterior pituitary is really an extension of the brain (the hypothalamus).

Question 4

The Pituitary gland is positioned in the sella turcica at the base of the skull…the pituitary is comprised of:

Answer 4

1. The anterior pituitary, or adenohypophysis, made up of the pars distalis, pars intermedia, and pars tuberalis.
2. The posterior pituitary, or pars nervosa (or infundibular process), the infundibular stem or stalk, and the median eminence.

Question 5

What is the Anterior and Posterior Pituitary derived from?

Answer 5

a. The anterior pituitary is derived embryonically from an outgrowth of endoderm called Rathke’s pouch
b. While the posterior pituitary is really an extension of the brain (the hypothalamus).

Question 6

Anterior Pituitary-Pars Distalis

Large Overview

Answer 6

a. Pars Distalis: The anterior pituitary is composed of cells that synthesize and release growth hormone (GH), prolactin (PRL), adrenocorticotropin (ACTH) and derivatives, thyroid stimulating hormone (TSH), and two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH).

b. Five types of cells have been identified in various mammalian species.
These are:
1. Somatotrophs (GH)—make up about 50 % of the secretory cells.
2. Lactotrophs (PRL)—make up about 20%
3. Gonadotrophs (FSH, LH) about 5-10%
4. Corticotrophs (ACTH), about 15-20%
5. Thyrotrophs (TSH), about 5-10%

c. These cells synthesize, store, and release respective hormones in granules.
i. Individual cell types can be identified immunocytochemically by light microscopy using antibodies to specific hormones:
ii. In early histology three classes of cells were observed based on dye staining: acidophils (containing either GH or PRL), basophils (containing TSH, ACTH or LH and FSH) and chromophobes—cells lacking granules which are thought to be in a resting state or may have been degranulated.

d. There is an extensive vasculature of small vessels/capillaries/sinusoids within the pars distalis.
i. The hormone-secreting cells are arranged in rows around capillary endothelial cells that are fenestrated to allow rapid passage of hormones out from the various endocrine cells, but also enables diffusion towards the cells of releasing factors transported via the hypophyseal portal system
ii. This enables reasonably rapid hormonal responses by fast passage into/out of the capillary sinusoids of the anterior pituitary.

Question 7

Extensive Vasculature of the Pars Distalis

portion of the Anterior Pituitary Gland

Answer 7

a. There is an extensive vasculature of small vessels/capillaries/sinusoids within the pars distalis (anterior pituitary)
b. The hormone-secreting cells are arranged in rows around capillary endothelial cells that are fenestrated to allow rapid passage of hormones out from the various endocrine cells, but also enables diffusion towards the cells of releasing factors transported via the hypophyseal portal system
c. This enables reasonably rapid hormonal responses by fast passage into/out of the capillary sinusoids of the anterior pituitary.

Question 8

Hypophyseal portal system

Answer 8

a. The hypophyseal portal system is a system of blood vessels in the brain that connects the hypothalamus with the anterior pituitary.
b. Its main function is the transport and exchange of hormones to allow a fast communication between both glands.
c. The fenestrated structure of capillaries in the hypophyseal portal system facilitates a rapid exchange between the hypothalamus and the pituitary, with only a small amount of hormones needed to stimulate an accurate effect in the respective target organs in the body.

Question 9

Anterior Pituitary- Pars Tuberalis and the hypophyseal portal system:

Answer 9

Pars Tuberalis and the hypophyseal portal system:

a. A collar of cells around the infundibular stalk contains blood vessels that lead from capillaries of the median hypothalamic eminence to small vessels/capillaries of the pars distalis.
i. The blood entering the median eminence comes from the superior hypophyseal arteries (from the internal carotid).

b. The capillaries of the median eminence thence lead to larger vessels in the tuberalis that deliver regulatory peptides (the releasing factors) secreted by hypothalamic neurons to the cells in the anterior pituitary.
c. These include TSH-releasing hormone (TSH-RH), gonadotropin releasing hormone (GNRH), corticotropin releasing hormone (CRH), growth hormone releasing hormone (GHRH) and the inhibitory factors, somatostatin and dopamine.

d. Thus, this tiny portal systems provides an intimate vascular linkage between hypothalamic neurons and endocrine cells of the anterior pituitary.
i. Blood leaves the anterior and posterior pituitary via small hypophyseal veins.

Question 10

Pars Distalis, Pars Tuberalis, and Pars Intermedia

Answer 10

a. The pars distalis, (distal part), comprises the majority of the anterior pituitary and is where the bulk of pituitary hormone production occurs.
i. The pars distalis contains two types of cells including chromophobe cells and chromophil cells.
ii. The chromophils can be further divided into acidophils (alpha cells) and basophils (beta cells).
iii. These cells all together produce hormones of the anterior pituitary, and release them into the blood stream.

b. Pars tuberalis
i. The pars tuberalis, (tubular part), forms a part of the sheath extending up from the pars distalis which joins with the pituitary stalk (also known as the infundibular stalk or infundibulum), arising from the posterior lobe.
- (The pituitary stalk connects the hypothalamus to the posterior pituitary).
ii. The function of the pars tuberalis is poorly understood.
iii. However it has been seen to be important in receiving the endocrine signal in the form of TSHB (a β subunit of TSH) informing the pars tuberalis of the photoperiod (length of day).
iv. The expression of this subunit is regulated by the secretion of melatonin in response to light information transmitted to the pineal gland

c. Pars intermedia
i. The pars intermedia, (intermediate part), sits between the pars distalis and the posterior pituitary, forming the boundary between the anterior and posterior pituitaries.
ii. It is very small and indistinct in humans.

Question 11

Function of the Anterior Pituitary Gland

Answer 11

a. The anterior pituitary contains five types of endocrine cell, and they are defined by the hormones they secrete:
i. somatotropes (GH)
ii. prolactins (PRL)
iii. gonadotropes (LH and FSH)
iv. corticotropes (ACTH)
v. and thyrotropes (TSH)

b. Hormones secreted by the anterior pituitary are trophic hormones and tropic hormones.
i. Trophic hormones directly affect growth either as hyperplasia or hypertrophy on the tissue it is stimulating.
ii. Tropic hormones are named for their ability to act directly on target tissues or other endocrine glands to release hormones, causing numerous cascading physiological responses

Question 12

Hypothalamus and Anterior Pituitary

Answer 12

a. In the hypothalamic–adenohypophyseal axis, releasing hormones, are released from the median eminence, a prolongation of the hypothalamus, into the hypophyseal portal system, which carries them to the anterior pituitary where they exert their regulatory functions on the secretion of adenohypophyseal hormones.

b. These hypophysiotropic hormones are stimulated by parvocellular neurosecretory cells located in the periventricular area of the hypothalamus.
i. After their release into the capillaries of the third ventricle, the hypophysiotropic hormones travel through what is known as the hypothalamo-pituitary portal circulation.

c. Once they reach their destination in the anterior pituitary, these hormones bind to specific receptors located on the surface of pituitary cells.
i. Depending on which cells are activated through this binding, the pituitary will either begin secreting or stop secreting hormones into the rest of the bloodstream.

Question 13

Five types of cells have been identified in various mammalian species for the Anterior Pituitary-

Answer 13

a. These are:
1. Somatotrophs (GH)—make up about 50 % of the secretory cells.
2. Lactotrophs (PRL)—make up about 20%
3. Gonadotrophs (FSH, LH) about 5-10%
4. Corticotrophs (ACTH), about 15-20%
5. Thyrotrophs (TSH), about 5-10%

b. These cells synthesize, store, and release respective hormones in granules. Individual cell types can be identified immunocytochemically by light microscopy using antibodies to specific hormones
c. In early histology three classes of cells were observed based on dye staining: acidophils (containing either GH or PRL), basophils (containing TSH, ACTH or LH and FSH) and chromophobes—cells lacking granules which are thought to be in a resting state or may have been degranulated.

Question 14

Posterior Pituitary (pars nervosa)

Overview Summary

Answer 14

a. The posterior pituitary is essentially an extension of the hypothalamus.

b. The hormones, antidiuretic hormone (ADH, vasopressin) and oxytocin, are released from the ends of axons that arise from cell bodies of neurons present in the hypothalamus.
i. These axons are unmyelinated and comprise a bundle that extend alongside one another within the infundibular stalk.

c. There are also nuclei that can be observed within the posterior pituitary that are the nuclei of pituicytes, which are supportive astrocyte-like glial cells (not producing hormones).
d. The axons expand into bulbous structures that contain neurosecretory vesicles (Herring’s bodies).

e. Hormones are produced in the hypothalamus (in the cell bodies) as large polypeptides that undergo cleavage during vesicular transport down the axons.
i. The prohormones are called vasopressin-neurophysin and oxytocin-neurophysin (more in physiology).

f. Vasculature in the posterior pituitary is evident, but is not as extensive as in the anterior pituitary.

Question 15

Posterior Pituitary Nerve Layout

Answer 15

The posterior pituitary is essentially an extension of the hypothalamus.

a. The hormones, antidiuretic hormone (ADH, vasopressin) and oxytocin, are released from the ends of axons that arise from cell bodies of neurons present in the hypothalamus.
i. These axons are unmyelinated and comprise a bundle that extend alongside one another within the infundibular stalk.

b. There are also nuclei that can be observed within the posterior pituitary that are the nuclei of pituicytes, which are supportive astrocyte-like glial cells (not producing hormones).
i. The axons expand into bulbous structures that contain neurosecretory vesicles (Herring’s bodies).

Question 16

Posterior pituitary Brief Summary

Answer 16

a. The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system.

b. The posterior pituitary is not glandular as is the anterior pituitary.
i. Instead, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary which serves as a site for the secretion of neurohypophysial hormones (oxytocin and vasopressin) directly into the blood.

c. The hypothalamic–neurohypophyseal system is composed of the hypothalamus (the paraventricular nucleus and supraoptic nucleus), posterior pituitary, and these axonal projections

Question 17

Posterior Pituitary Structure and Function

Answer 17

a. The posterior pituitary consists mainly of neuronal projections (axons) of magnocellular neurosecretory cells extending from the nuclei of the hypothalamus.
i. These axons store and release neurohypophysial hormones oxytocin and vasopressin into the neurohypohyseal capillaries, from there they get into the systemic circulation (and partly back into the hypophyseal portal system).

b. In addition to axons, the posterior pituitary also contains pituicytes, specialized glial cells resembling astrocytes assisting in the storage and release of the hormones

c. Hormone secretion
i. Two hormones are classically considered as being related to the posterior pituitary: oxytocin and vasopressin.
ii. These hormones are created in the hypothalamus and released in the posterior pituitary.
iii. After creation, they are stored in neurosecretory vesicles regrouped into Herring bodies before being secreted in the posterior pituitary into the bloodstream.

Question 18

The Thyroid Gland

Answer 18

a. The thyroid is a multi-lobed gland comprised of a series of follicles, each having a single layer of epithelial cells surrounding a central chamber referred to as the colloid.
b. The epithelial cells are producers of the colloid and ultimately the thyroid hormone group.

c. The gland is notable for its tremendous storage capability of potential hormone in the colloid.
i. Scattered cells between follicles produce calcitonin.

d. Extensive vascularization around the follicles enables iodide pumping from the blood and conversion to iodine by the epithelial cells and release of the thyroid hormones into the blood.
i. The epithelium also synthesizes and secretes the protein thyroglobulin into the interior of the follicle and takes up and digests thyroglobulin to generate the thyroid hormones.

e. The iodide pump is very effective.
i. Within a few minutes a major portion of radioactive iodide is taken up by the thyroid making it possible to perform partial thyroidectomies.

f. Thyroglobulin is a large protein rich in tyrosine residues, which are the sites of iodination and modification to generate the thyroid hormones.

Calcitonin “C” cells have secretory granules containing calcitonin, a small protein. This hormone decreases release of calcium from bones (down regulates osteoclastic activity). It appears to act oppositely to parathyroid hormone which (below) is centrally involved in increasing blood calcium levels.

Question 19

Thyroid Gland Vascularization

Answer 19

a. Extensive vascularization around the follicles enables iodide pumping from the blood and conversion to iodine by the epithelial cells and release of the thyroid hormones into the blood.
b. The epithelium also synthesizes and secretes the protein thyroglobulin into the interior of the follicle and takes up and digests thyroglobulin to generate the thyroid hormones.

Question 20

Thyroglobulin and the generation of thyroid hormones in the Thyroid Gland

Answer 20

a. Thyroglobulin is a large protein rich in tyrosine residues, which are the sites of iodination and modification to generate the thyroid hormones.
b. TSH stimulates synthesis of thyroglobulin and its uptake and breakdown from the colloid with consequent release of thyroid hormone (T3 and T4, containing, respectively, 3 or 4 iodine atoms per molecule) into the blood.
c. Colloid droplets are taken up and processed in the interior of the epithelial cells by the lysosomal system resulting in production of thyroid hormones.

Question 21

Calcitonin of the Thyroid Gland

Answer 21

a. Calcitonin “C” cells have secretory granules containing calcitonin, a small protein.
i. This hormone decreases release of calcium from bones (down regulates osteoclastic activity).

b. It appears to act oppositely to parathyroid hormone which (below) is centrally involved in increasing blood calcium levels.

Question 22

The Parathyroid Glands

Answer 22

a. The parathyroids are closely associated with the thyroid gland, and 4 to 8 may be present in any individual.

b. They contain three main cell types:
(1) Chief cells, which produce parathyroid hormone (PTH), a protein of 84 amino acids.
i. It increases osteoclast release of calcium from bone, and increases calcium uptake in the GI tract and by the kidney, which elevates calcium levels.
(2) Oxyphil cells, which contain a number of mitochondria, usually stain paler but whose functional significance remains unknown
(3) Adipose cells.

c. Blood vessels are seen, although are not as extensive as observed, for instance, in the anterior pituitary or islets of Langerhans.

Question 23

The Adrenal Gland

Answer 23

a. The adrenal gland, like the pituitary, is a dual origin gland, housing two organs, physically distinct as the cortex and the medulla.
b. The cortex produces and releases various steroids whereas the medulla produces and releases amino acid derived hormones including epinephrine, norepinephrine and enkephalins.

c. Blood is delivered via the superior, middle and inferior suprarenal arteries, which branch and enter through the capsule via short cortical arteries into an outer subcapsular arterial plexus.
i. Blood then passes via an anastomosing network of capillaries into the medullary region.

d. Other arteries (long cortical arteries) take blood to medullary region more directly, with the blood ultimately entering a series of small capillaries/sinuosoids to the central medullary vein, which drains via the suprarenal vein.

Question 24

Cell types of the Parathyroid Hormone

Answer 24

1. Chief cells, which produce parathyroid hormone (PTH), a protein of 84 amino acids.
   i. It increases osteoclast release of calcium from bone, and increases calcium uptake in the GI tract and by the kidney, which elevates calcium levels.
2. Oxyphil cells, which contain a number of mitochondria, usually stain paler but whose functional significance remains unknown
3. Adipose cells

Question 25

Cortex of the Adrenal Gland

Answer 25

a. The cortex is divided into three layers, labeled, respectively, from outer to inner cortex layers as zones: the zona glomerulosa, the zona fasciculata, and the zona reticularis.

b. The zones look different histologically and are associated with different classes of steroids as follows:
1. Zona glomerulosa: mineralocorticoids, most notably aldosterone
2. Zona fasciculata: glucocorticoids such as cortisol
3. Zona reticularis: Androgens of modest potency.

c. These cells are all involved in lipid/steroid metabolism thus are high in relative lipid content.
i. The fasciculata is especially rich in large lipid droplets.
ii. The cells are arranged in vertical columns separated by capillaries/small sinusoids that drain to the medulla.
iii. The fasciculata and reticularis are controlled by ACTH whereas the glomerulosa is regulated through the angiotensin system. Mitochondria of cortical cells have tubular cristae characteristic of steroidogenic cells.

Question 26

The zones of the Adrenal Cortex

Answer 26

a. The zones look different histologically and are associated with different classes of steroids as follows:
1. Zona glomerulosa: mineralocorticoids, most notably aldosterone
2. Zona fasciculata: glucocorticoids such as cortisol
3. Zona reticularis: Androgens of modest potency.

b. These cells are all involved in lipid/steroid metabolism thus are high in relative lipid content.
i. The fasciculata is especially rich in large lipid droplets.

c. The cells are arranged in vertical columns separated by capillaries/small sinusoids that drain to the medulla.
d. The fasciculata and reticularis are controlled by ACTH whereas the glomerulosa is regulated through the angiotensin system.
e. Mitochondria of cortical cells have tubular cristae characteristic of steroidogenic cells.

Question 27

The Adrenal Medulla

Answer 27

a. The adrenal medulla contains epinephrine (adrenalin) and norepinephrine (noradrenalin) producing cells.
b. They are arranged as clusters around venous channels/sinusoids that drain toward the central medullary vein.
c. They are under sympathetic and parasympathetic control.
d. Enkephalins and chromogranins are also released by these cells.
* More will be discussed in physiology concerning their control of release.