Endocrine Development - Bolender

Question 1

1. In general, both endocrine and exocrine glands are derived from what type of embryonic tissue?
2. What second tissue type does the former invade into during the gland’s development?

Answer 1

1. Embryonic epithelium
2. The adjacent mesenchyme

Question 2

What components of the mature gland are derived from mesenchyme?

Answer 2

The connective tissue components of the capsule and any subdivisions of the gland

Question 3

1. As a generalized rule of thumb, when do the endocrine glands begin their formation?
2. When do they begin to release their hormones?

Answer 3

1. The embryonic period
2. Early in the fetal period
   
   • Initial hormone products from fetal glands may be very small or just biologically inactive

Question 4

1. What are the two primordia that the pituitary gland is derived from?
2. What germ layer do each of these primordia originate from?

Answer 4

1. Primordia:
   
   • Hypophyseal Diverticulum (HD), aka Rathke’s Pouch
   • Infundibulum
2. Both primordia are ectoderm-derived
   
   • HD is oral ectoderm
   • Infundibulum is neural ectoderm

Question 5

The HD / Rathke’s Pouch begins as a **placode **that evaginates cranially to form the pouch.

1. Following folding in the sagittal plane, where is this placode located in the embryo?
2. When does the placode evaginate?
3. What tissue type does it evaginate into?

Answer 5

1. Within the surface ectoderm that will form the roof of the oral cavity. Specifically, in the midline just ventral to the oropharyngeal membrane.
2. Week 3
3. Surrounding mesenchyme

Question 6

When does the HD / Rathke’s Pouch lose its connection with the oral cavity?

Answer 6

(Toward the end of) Week 8

Question 7

1. Formation of the HD / Rathke’s Pouch is mediated by what two signalling molecules?
2. What additional signalling molcule promotes proliferation and survival of HD epithelial cells?

Answer 7

1. BMP-4 and FGF-8
2. Hesx-1

Question 8

1. Which half of the pituitary gland is derived from the HD / Rathke’s Pouch?
2. What is an alternative name for this part of the pituitary?

Answer 8

1. Anterior pituitary
2. Adenohypophysis

Question 9

• What three parts make up the mature anterior pituitary?
• How is each part formed from the immature HD / Rathke’s Pouch?

Answer 9

1. Pars Distalis
   
   • Expansion / thickening of the anterior wall of the HD
   • Note: Comprises the bulk of the mature anterior pituitary
2. Pars Tuberalis
   
   • A small superior extension
   • Grows along the infundibulum (stalk) of the neurohypophysis and eventually surrounds it
3. ​Pars Intermedia
   
   • Forms from the posterior wall of the HD
   • Small and indistinct in humans (Wiki)

Question 10

1. When does the pars tuberalis begin to form?
2. When does it surround the infundibulum?

Answer 10

1. Week 11
2. Week 16

Question 11

While observing a microscope section of a mouse pituitary, you notice a small, slit-like gap between the pars distalis and pars intermedia. What are you looking at?

Answer 11

The remnant of the original HD lumen

Question 12

What signalling molecule(s) is/are expressed in the following anterior pituitary cells?

1. Somatotrophs
2. Gonadotrophs
3. Melanotrophs

Answer 12

1. PIT-1 & Wnt
2. SF-1
3. HES-1

Question 13

When can ACTH be first detected in pituitary cells?

LH/FSH?

[Likely (hopefully) low yield]

Answer 13

ACTH: Week 8

LH/FSH: Week 10

Question 14

1. The infundibulum is an inferior midline diverticulum in the floor of what embryonic tissue?
2. When does the infundibulum form?

Answer 14

1. The diencephalon
2. Week 3

Question 15

When are the neurovascular links between hypothalamus and pituitary established by?

Answer 15

Week 12

Question 16

What is the result of deficient migration / evagination of Rathke’s Pouch?

Answer 16

A pharyngeal hypophysis

(aka, pituitary gland in the roof of your mouth. Not good.)

Question 17

1. What is the name for a tumor that froms from the remnants of the HD / Rathke’s Pouch?
2. Where (in the head) does this tumor form?
3. What symptoms can arise from the mass of the tumor itself?

Answer 17

1. Craniopharyngioma
2. Typically in the sella turcica
3. Symptoms:
   
   • Impingement of optic chiasm –> vision problems
   • Impingement of pituitary itself –> pituitary dysfunction
   • Hydrocephalus
     
     • Tumor mass blocks the flow of CSF through the ventricular system, causing an accumulation that increases ICP

Question 18

What type of tissue does the thyroid gland originate from? Where is this precursor located and what is it called?

Answer 18

A midline invagination of pharyngeal endoderm, called the Thyroid Diverticulum

Question 19

1. When is the thyroid diverticulum first visible?
2. Where does it extend?

Answer 19

1. Week 4
2. Inferiorly from the floor of the pharynx, between the median tongue bud and copula

Question 20

1. What structure connects the migrating thyroid diverticulum to the pharynx during development?
2. When does this connecting structure dissapear?
3. What remnant of this structure can be found in an adult?

Answer 20

1. Thyroglossal Duct
2. ~Week 11
3. Foramen cecum of the adult tongue

(N.B. Part of the duct may persist as a “pyramidal” lobe of the thyroid)

Question 21

As the thyroid diverticulum is displaced inferiorly, does it pass anterior or posterior to the hyoid bone?

Answer 21

Anterior

Question 22

1. When does the thyroid arrive at its final location?
2. Where is this location in relation to the cricoid cartilage?
3. Which cartilages of the trachea does the mature thyroid lay anterior to?

Answer 22

1. Week 7
2. Inferior
3. Cartilages 2 & 3

Question 23

1. When are follicles visible in the thyroid?
2. When do the follicle cells begin to produce complete thyroid hormone?

Answer 23

1. By Week 10
2. By the end of Month 3

Question 24

1. What primordia to the ultimopharyngeal bodies originate from?
2. What tissue are the bodies invaded by prior to their migration to the thyroid?
3. Once the bodies reach the thyroid, they disperse within the gland and form what cells?
4. What do these cell produce again?

Answer 24

1. 4th pharyngeal pouch
2. Neural crest
3. Parafollicular cells / C cells
4. Calcitonin (reduces plasma Ca²⁺)

Question 25

What aberrant formation can develop **within the remnants of the thyroglossal** **duct**? What are two complications of these formations?

Answer 25

Cysts Rupture or form a fistula to the skin

Question 26

1. Where can aberrant thyroid tissue be found? 2. Where is it most common?

Answer 26

1. Anywhere along the path of thyroid primordia displacement 2. Base of the tongue

Question 27

The **two sets** of parathyroid glands form from which primordia? ***Be specific.***

Answer 27

* The **_superior_** pair of parathyroids originates from the **dorsal wing** of each **_4th_ pharyngeal pouch** * The **_inferior_** pair of parathyroids originates from the **dorsal wing **of each **_3rd_ pharyngeal pouch** **_NOTE THE UNINTUITIVE SPATIAL RELATIONSHIP_**. The superior pair ***begins more caudally*** than the inferior pair, but ***ends more cranially***.

Question 28

When is it possible to start seeing parathyroid cells in the pharyngeal pouches?

Answer 28

Week 5

Question 29

Where can aberrant parathyroid tissue be found?

Answer 29

Analagously to the thyroid - **anywhere along the parathyroid's path of inferior displacement**

Question 30

1. The adrenal cortex originates from which cells? 2. When does this occur?

Answer 30

1. Coelomic epithelial cells on the medial side of the urogenital ridge 2. Weeks 4-5

Question 31

What transcription factor is expessed in adrenal cortex precursor cells?

Answer 31

SF-1 (Steroidogenic Factor-1)

Question 32

During the formation of the adrenal cortex, **two successive waves** of precursor cells enter the surrounding mesenchyme. 1. Following the migration of both waves, what is the spatial relationship between the two sets of cells? 2. What structure does the primary wave eventually form? 3. What structure does the second wave eventually form?

Answer 32

1. The **second** wave **surrounds** the **primary** wave. 2. Primary wave --\> **Fetal adrenal cortex** 3. Second wave --\> **Adult adrenal cortex** * (Yes, all of it. The zonas glomerulosa, fasciculata, and reticularis.)

Question 33

By week 9, a capsule of what tissue type surrounds each adrenal primordium?

Answer 33

Mesenchyme

Question 34

Compare the sizes of the fetal and adult adrenal cortexes.

Answer 34

* During development, the fetal cortex takes up 80% of the volume of the entire (fetal) adrenal gland * The adult cortex, in contrast, is 1/20th the size of the fetal cortex and takes up a much smaller proportion of the entire (adult) adrenal gland

Question 35

1. Which cells of the **placenta** stimulate the adrenal cortex during **early** development? 2. What protein does this cell type secrete to accomplish this stimulation? 3. What stimulates the adrenal cortex **later** in development?

Answer 35

1. Trophoblasts 2. hCG 3. ACTH from the fetal pituitary!

Question 36

Why is the fetal adrenal cortex unable to produce the sex hormones progesterone and androstenedione? What does the fetus rely on to produce these hormones instead?

Answer 36

The fetal cortex lacks **3ß-hydroxysteroid dehydrogenase** The placenta produces these hormones instead

Question 37

1. When does the fetal adrenal cortex completely involute? 2. When does the definitive adrenal gland reach its normal size?

Answer 37

1. By six months to one year of age (postnatal) 2. By two years of age

Question 38

What is mean by the term "Maternal-Fetal-Placental Unit" in terms of endocrine development?

Answer 38

The mother, fetus, and placenta all cooperate to produce the requisite steroid hormones for the fetus. While the placenta produces many steroids for the fetus, it cannot produce many **precursors**. The fetus and mother's body increase production of **weak androgens**, which the placenta's **aromatase** enzyme allows for conversion to **estrogens**.

Question 39

The adrneal **medulla** is derived from which cell type? What is the name for the mature cells derived from these precursors? What signal is believed to play a role in differentiating the precursor cells into the mature cells?

Answer 39

Neural crest Chromaffin Cells Gucocorticoids from the adjacent adrenal cortex

Question 40

The adrenal medulla is supplied by ***(sympathetic / parasympathetic)***, ***(preganglionic / postganglionic)*** nerve fibers that are also of neural crest origin.

Answer 40

sympathetic, preganglionic

Question 41

What is the pathogenesis of **Congenital Adrenal Hyperplasia****?** Which part of the adrenal gland englarges and why?

Answer 41

* Mutation in enzyme needed for cortisol and/or aldosterone * Mostoften **21-hydroxylase** * The cortex redirects the excess steroid precursors into **androgen production** * Increased **ACTH** from the pituitary causes hyperplasia * Loss of negative feedback from cortisol and/or aldosterone

Question 42

How does **Congenital Adrenal Hyperplasia** present in boys? In girls?

Answer 42

* Boys: * Early development of secondary sex characteristics * Girls: * Early virilization of the forming external genitalia * Results in **ambiguous genitalia** at birth

Question 43

Where is the pineal gland located in relation to the thalamus?

Answer 43

Superior to the thalamus

Question 44

What does the pineal gland secrete? When? How does the pineal gland affect the pituitary gland?

Answer 44

Melatonin Usually at night Melatonin **inhibits the pituitary-gonadal axis**

Question 45

How does the pineal gland form? When is it visible by?

Answer 45

It begins as a **midline, dorsal diverticulum** of the **roof of the diencephalon** Visible by about 10 weeks

Question 46

Which of the three germ layers primarily makes up each of the following endocrine glands? Which glands also contain neural crest? 1. Pituitary 2. Thyroid 3. Parathyroid 4. Adrenal

Answer 46

1. Pituitary: **Ectoderm** (two layers) 2. Thyroid: **Endoderm** (**+ neural crest**) 3. Parathyroid: **Endoderm** 4. Adrenal: **Mesoderm** (**+ neural crest** (medulla))

Question 47

Which bone of the skull does the pituitary gland untimately reside in?

Answer 47

Sphenoid