Endocrinology lecture: Reproductive cancers Nov 28

Causes of male infertility

 Acrosomal defect in sperm
o Acrosome should cover at least 55% of the pronucleus

Cancers of endocrine glands

 Excess of a hormone showing up in a blood test
 Parathyroid cancer  elevated calcium levels
o Follow up of measure of parathyroid hormone

Ex. Cushing
 Dex suppression test (Dexsomethosone)
 Give a synthetic agonist of cortisol to test the feedback loop
 Should be able to suppress the secretion of cortisol, by suppressing the secretion of
ACTH.
 Cortisol measured in saliva (filtrate of plasma)
o Pretty reliable method of measurement
o In adrenal hyperplasia, you should get a positive reaction to the dex
suppression test
o Not responsive means it’s probably a tumor
o Before a tumor becomes malignant, it will make its presence known,
which is the advantage of having an endocrine cancer
 In animal studies, the andogenist cortisol is corticosterone, but squirrels have
cortisol which is the exception.
 Depending on the results you get from the test you do more follow up.

Diabetes test:
 Test status of patient’s islets capacity to produce insulin
 C - peptide

SERM (Selective estrogen receptor modifier)

o Tamoxifen  anti-estrogen in breasts
 Has some estrogen agonist effects in bone
 Basically like putting you in extreme menopause
 Most places where estrogen binds, it will outcompete

Immunoreactive vs. biologically reactive

Epithelial cells  adenoma  adenocarcinoma

Stromal  sarcoma

Why doesn't a tumor respond to a dex suppression test?

Ovarian cancer:
 Less common than breast cancer
 Asymptomatic
Endocrinology lecture: Reproductive cancers Nov 28

 How do you know you have ovarian cancer? It starts effecting other parts of the
body (Ovaries in open cavity  easy for tumors to spread)
 Screening is really tough
 How is it detected?

Two stage carcinogenesis:

Injury  inflammation in cells that are not supposed to do mitosis all the time.
Stage 1: initiation
 Mutagenesis (mutation of the cells)
o Become aneuploidy
o Lots of genes become activated or turned off
o Cancer cell: Mutates to the extent where it no longer expresses normal
controls
o Turns cell into a parasite
Stage 2: promotion
 Mitogenesis
o Makes the cell aggressive

Breast cancer example:

HER-2 (+): receptor for epidermal growth factor (EGF)

Don't need estrogen in order to be stimulated to grow
The more that the tumor cell becomes like a germ cell, the greater the capacity to escape
controls

TNBC:

Problem with breast cancer: estrogen can be metabolized into a promotor or initiator in
cancer

Ductal cytonoma:
 Non-cancerous

In ovulation you can see inflammatory markers because it is an explosive event

Also get inflammatory markers due to monthly menstruation  endometrium
Luteal phase  breast tissue (minigrowth and regression)

Stomach cancer
 H. plyori
 Inflammation

Asbestos  mesothelioma
Due to inflammation

Reciprocal relationship between glycine and methionine

Endocrinology lecture: Reproductive cancers Nov 28

 cancer cells are methionine dependent, rid cancer by lowering methionine

B16-melonoma  grows reliably unless you supplement glycine

Reproductive cancers:
Incidence of cancers in men and women is about the same.

Female
 Breast (most common)
 Cervix/uteri
o HPV (sexually transmitted)
 Ovarian (do not notice the difference)
 Endometrial

Male
 Prostate (most common)
o Once you get up to about 90 years old, the incidence of prostate insitu is
almost 100%.
 Testicular cancer (Lance Armstrong effect  produces abundance of androgens)
o Makes presence known months or years before it’s dangerous.

Female breast cancer:

 Lobules type 1, 2, 3, and 4
 Once any type of cell is terminally differentiated, it cannot be stimulated to divide
o Cannot be turned into a breast cancer cell
o Susceptibility window  time between puberty and first term pregnancy
o In puberty your breasts grow but they do not differentiate to produce milk.
o Once you have your first child you have type 3 and 4 lobules.
o But mainly the susceptibility window is closed after first child
 Big difference in susceptibility window: how much tissue do you have
that is vulnerable and for how long?
 Model cancer susceptibility based on this
 Ionizing radiation is a primary carcinogen

Cervical lining  more conducive to viral transmission

 Synergistic effects of HPV