Developmental Endocrinology

Question 1

Indirect (complex life cycle)

Answer 1

Discontinuous development, with a larval stage followed by a metamorphosis to the juvenile adult form (ancestral)

Question 2

Direct

Answer 2

Continuous development from fertilized egg to juvenile adult (derived)

Question 3

Direct development / Maternal care evolved…

Answer 3

Many times. Not from one, common ancestor.

Question 4

Early development (DIRECT) in mammals involves chemical mediation that is…

Answer 4

Paracrine

Question 5

Post-embryonic development (after circulatory system develops) [DIRECT] is…

Answer 5

Paracrine and hemocrine.

Question 6

Sources of hormones in mammalian development.

Answer 6

Fetus, mother, placenta

Question 7

How can people study direct development?

Answer 7

• Congenital glandular deficiencies (mutation / non-developing gland)
• fetal surgeries (ablations and replacement)
• in vitro cultures (hard for mammalian tissues, easy for ectoderms)
• renal capsule grafting
• transgenic animals

Question 8

What is renal capsule grafting?

Answer 8

Method for growing embryonic or neonatal organ rudiments in vivo for extended periods.

-Organ is hidden inside the kidney (underneath a graft / cut). Cannot be used for an embryo / something larger.

Question 9

Name all the organs and the hormones involved in postnatal growth.

Answer 9

pituitary: GH, TSH
thyroid: T3, T4
liver: IGFs
pancreas: insulin
gonads: E2 and T

Question 10

What is T3 / T4 necessary for?

Answer 10

Skeletal and neurological growth.

Question 11

What are E2 and T necessary for?

Answer 11

Brain, secondary sex characteristics, urogenital tract.

Question 12

Growth hormone is not necessary for fetal growth, but later development. Gigantism can be caused by:

Answer 12

• Growth hormone secretion
• Growth hormone action
• Insulin-like growth factors

Question 13

What are the most important hormones involved in prenatal growth and development?

Answer 13

• Thyroid hormones: brain and skeletal development
• Glucocorticoids: lung development, brain development
• Sex Steroids: CNS development, genital tract, sex accessory organs

Question 14

Humans become dependent on TH for skeletal growth at or just before…

Answer 14

Birth

Question 15

____ is the predominant mediator of TH action on the bone.

Answer 15

TRα1

Question 16

Bone also expresses TSH receptor. But TSH…

Answer 16

Is a negative regulator of bone turnover.

Question 17

When a mutant strain is developed for TRα(0/0)…

Answer 17

You get tissue hypothyroidism. (The infrastructure is there, the ‘hollowness’ but the lining is thicker)

Question 18

When a mutant strain is developed for TRβ(-/-)…

Answer 18

You get hyperthyroidism / loss of extensive bone infrastructure (aka ‘hollowness’).

Question 19

Thyroid hormone is required for proper development of the nervous system. Think of some negative examples.

Answer 19

Rat cerebellar Purkinje cells, and the cerebellum.

Question 20

Name the ‘pleiotropic effects’ of thyroid hormone on the developing brain.

Answer 20

• cell proliferation
• cell migration
• cell differentiation
• neural circuit formation
• neuronal morphogenesis (dendrite elaboration and branching, synaptogenesis)
• myelination

Question 21

What does it mean that thyroid hormone induces cascades of gene regulation during development?

Answer 21

-Thyroid hormone represses DNA transcription, but when it’s activated…

It trades a co-repressor complex for a co-activator complex, and the PRIMARY RESPONSE GENES are transcription factors which affect SECONDARY RESPONSE GENES.

Question 22

Thyroid hormone has an initial signal which is ______.

Answer 22

Amplified, and the gene regulation programs are tissue-specific.

Question 23

Which thyroid hormone-induced transcription facotr mediates thyroid hormone action on neuronal develppment?

Answer 23

Kruppel-like factor 9 (KLF9); from the family of Kruppel like, specificity proteins.

Question 24

Forced expression of KLF9 induces ______ in neural cells.

Purkinje cell layer of cerebellum in mice that were knocked out for ______

Answer 24

Neurite outgrowth (extension of branched networks).

*KLF9

Question 25

What are the hormones involved in 'prenatal' growth and development?

Answer 25

* Insulin: produces a favorable metabolic environment * IFGs: IGF-I and IGF-II * Placental polypeptides (placental lactogen; placental GH; hCG) * Other peptide growth factors: most involved with early growth and development

Question 26

IGF - ____ is most important for postnatal development. *What disorder demonstrates this?

Answer 26

I; it has a c-domain which is not cleaved off. *Leprechaunism- individuals are resistant to IGF-I because of IGF-I receptor deficiency. Pygmies give birth to normal size infants, yet they have an IFG-I deficiency [~>postnatal)

Question 27

In a __________ [indirect development] the animal begins life as a larva, then undergoes a ___________ to the juvenile adult form.

Answer 27

complex life cycle, metamorphosis

Question 28

Complex life cycles [indirect development] are found in...

Answer 28

invertebrates urochordates cephalochordates chordates (fishes and amphibians) *NOT in amniotes, reptiles, birds, mammals

Question 29

What is the history of metamorphosis in relation to marine life?

Answer 29

- Metamorphosis evolved in the sea - Metamorphosis life histories are wide-spread among marine invertebrate species - Larvae detect suitable 'settlement sites' via dissolved cues in the water

Question 30

Describe metamorphic transition in marine invertebrates:

Answer 30

* Developmental change - morphogenesis | * Ecological change - transition from plankton to benthos

Question 31

Describe key characteristics of chordate metamorphosis. *Name an example

Answer 31

Thyroid hormone induces metamorphosis, this means that the species must have a thyroid hormone receptor *Cephalochordate Amphioxus

Question 32

What is paedomorphosis? *Name an example

Answer 32

When animals become reproductively mature while retaining larval characteristics. Neoteny; aka adult retains juveniles characteristics. (Humans ~> flat face like babies) *Salamanders

Question 33

What do obligate paedomorphs do? *Name an example

Answer 33

They never metamorphose. *Necturus Maculosus (Mudpuppy): it has thyroid receptors in the brain for neural development, but none in the gill!

Question 34

What do facultative paedomorphs do?

Answer 34

They metamorphose if the aquatic environment deteriorates. *They can still be reproductively mature as larvae, and stress / CRH causes them to transform

Question 35

Describe flatfish metamorphosis. Larvae Adults

Answer 35

Larvae are limnetic (they live in the water column); and are bilaterally symmetical. Adults are benthic (live at sea bottom); during metamorphosis teh right eye migrates to the left side of the body and they become flatfish.

Question 36

How is eye migration mediated in flatfish metamorphosis?

Answer 36

Through proliferating epithelial and sub-epithelial cells (which are hyperactive on one side of the fish)

Question 37

What else undergoes a metamorphosis in flatfish?

Answer 37

Their stomach, their retina, their pigmentation (top must be dark to camouflage with the sea floor, the bottom must be light).

Question 38

Describe Salmonid Smoltification. And which one is the Parr / which one is the Smolt?

Answer 38

It is driven by the lengthening photoperiod in the spring. There is a surge in thyroid activity prior to smoltification. The timing is under the control of the lunar cycle; peak thyroid activity coincides with each successive new moon.

Question 39

Describe downstream migration in terms of emoltification / seawater adaptation?

Answer 39

During downstream migration plasma cortisol and GH increase; both are essential for seawater adaptation.

Question 40

Amphibian metamorphosis is instigated by _____ as proven in experiments where different organs (heart, liver, skeletal muscle, etc) were ground and given to tadpoles in vitro.

Answer 40

Thyroid Hormone

Question 41

Metamorphosis in amphibians is followed by... (Where do they peak?)

Answer 41

Increased production of thyroid hormone and its receptors... THEY PEAK at the metamorphic climax.

Question 42

A common theme in animal metamorphoses s...

Answer 42

That they are controlled by hydrophobic signaling molecules that bind to nuclear proteins (members of the nuclear hormone receptor superfamily).

Question 43

Insect metamorphosis is controlled by the steroid hormone _______. *What does it dimerize with?

Answer 43

Ecdysone; it heterodimerizes with ultraspiracle (USO), a homolog of vertebrate RXRs.

Question 44

Thyroid hormone can also induce metamorphosis in ________.

Answer 44

echinoderms (e.g., sea urchins, sand dollars). This can happen because the egg / larvae goes into a 'non-feeding larval life cycle.' Maybe... stress / CRH?

Question 45

Hypothalamus controls the timing of TADPOLE metamorphosis... how? (Hypothalamus used only one substance to make two from the pituitary)

Answer 45

It releases CRF, which goes to the anterior pituitary which then makes ACTH ( goes to interrenal / adrenal) and TSH (goes to thyroid) ACTH stimulates renal production of corticosterone and TSH stimulates production of T4.

Question 46

What does tissue remodeling / thyroid hormone involved?

Answer 46

Cell death, proliferation and differentiation. *Occurs in places like the brain, intestine, etc.

Question 47

Thyroid hormone controls the development of the major part of the retina in tadpoles / frogs... and...

Answer 47

The ipsilateral visual projections form the retina to the tectum. AKA: the tadpole must have panoramic views, because it has to see all around. Right ~> left side, and vice versa. The frog must have binocular views to find prey, both eyes go to both sides.

Question 48

Explain the increase in RXRα, TRα, and TRβ mRNA during the tadpoles aging / metamorphosis?

Answer 48

RXRα inc. first, then TRα following close behind. These two prime the initial response: 'cell proliferation.' TRβ mRNA inc-. later, because it does the actual cell migration, differentiation, and death. (It inc. near T3 and T4 surge)

Question 49

Autoinduction of TRβ is explained by....

Answer 49

A thyroid hormone response element (T3RE) located in the proximal promoter of the TRβ gene.

Question 50

What is nuclear receptor (NR) autoinduction?

Answer 50

When the ligand causes upregulation of its own receptor. (Like T3 on TRβ mRNA)

Question 51

What is necessary for NR autoinduction to generate a feed-forward response?

Answer 51

Positive feedback, (T3 must stimulate more T3 production) and this must end for autoinduction to stop.

Question 52

Name some examples of positive feedback on NR auto induction.

Answer 52

- Ovarian and uterine cycles: terminating event => ovulation | - Amphibian metamorphosis: terminating event => tissue transformation, biochemical and morphological maturation

Question 53

In tadpole metamorphosis corticosterone...

Answer 53

Increases D2 expression which diodinates T4 to T3.

Question 54

Why does the tadpole's tail degenerate last?

Answer 54

Because it's needed for the tadpole-like-frog to swim, and because it has less / is least sensitive to T.H.

Question 55

Overall, how do glucocorticoids synergize with T.H.?

Answer 55

1) GC inc. production of thyroid hormone receptors | 2) GC induces expression of deiodinase type 2 (Dio2) to activate thyroid hormone.

Question 56

Explain glucocorticoid and thyroid hormone synergy in mammalian development.

Answer 56

- Synergistic regulatino of intestinal enzymes - Synergy in promoting alveolar epithelia differentiation (fetal lung maturation) - Brain maturation and development is regulated by TH and is accelerated by stress hormones/intrauterine stress.

Question 57

What is the physio. / develop. purpose of thyroid and stress hormone synergy?

Answer 57

The production of glucocorticoids is influenced by the external and internal environments (i.e. stress) ~> mediators of environmental effects on the character & timing of development (developmental plasticity).