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CP450s; desmolase; 11A; estradiol

_______ are hydroxylating the C27 end (arm) of the cholesterol molecule. The molecule they form (20,22 - dihydroxy cholesterol) is then broken down to form the pregnenolone.

The CP40 used actually acts on C-20 and C-22 but it is an enzyme commonly referred to as ________ and it is a CYP__A.

The pregnenolone that iw formed can become progesterone or branch off and become an _________.

P450scc

The desmolase used to cleave cholesterol is now preferably called _______ (cholesterol side chain cleavage enzyme).

progesterone

Pregnenolone, made from cholesterol by P450scc can become _________.

17; 21

Progesterone can be hydroxylated in the __ or __ position. The former makes glucocorticoids, the latter makes mineralcorticoids. This is also done by different CP540s.

21l corticosterone; aldosterone; mineral

CYP11B2 can form hydroxylations an the same side.

__-Hydroxyprogesterone (deoxycorticosterone) is hydroxylated by CYP11B2 to form ___________. This is then hydroxylated again by the same CYP11B2 to form _____________ (_______corticoid).

17; 21; cortisone; gluco

__-hydroxyprogesterone uses CYP__ to become 17,21-Dihydroxyprogesterone. Then CYP11B1 turns it into ________ (______corticoid).

17

CYP21 is used in the synthesis of glucocorticoids and mineralcorticoids, but in glucocorticoids, CYP__ is used first.

inflammatory; immune

Cortisone (glucocorticoid) is anti__________. Prednisone is a drug that is a synthetic derivative or cortisone taken to dampen the ________ system.

p450scc

Def.: Cholesterol side chain cleavage enzyme converting cholesterol to pregnenolone. Utilizes O2 and NADPH.

11; desmolase; pregnenolone

p450scc, the cholesterol side chain cleavage enzyme, is actually CYP__A (used to be called ________) and this makes __________.

pregnenolone

Progesterone comes from _____________.

21

CYP__ hydroxylase is needed for mineral- and glucocortocoids (from progesterone).

True

T or F: Different CP450 MOs are involved in the interconversions to get to gluco- and mineralcorticoids.

estradiols

Instead of becoming progesterone, pregnenolone can go on to make sex hormones like _________.

21; short

Sex hormones are NOT dependent on __ hydroxylation. They are _____er analogs, and do not have the branchings that give you the larger numbers.

True

T or F: Women do have testosterone.

19; aromatic

Aromatase is a CYP__A1 that performs multiple oxidations to get an _________ ring seen in Estrone or Estradiol.

True

T or F: There are no 21-hydroxylations associated with the synthesis of sex hormones.

sex; glucocorticoids; mineralcorticoids

Metabolic Errors of Steroid Synthesis:

21-hydroxylase deficiency
- We still have the ability to make ____ hormones.
- We have inhibition of the production of ___________ and _________.

sex

When there is a deficiency in 21-hydroxylase, the body tries to compensate and there is an overabundance of ___ hormones.

Addison's

Addison's or Cushing's?:
Shows up quite frequently in the older population.

Addison's

Addison's or Cushing's?:
impaired adrenocortical function (hypofunction)

Addison's

Addison's or Cushing's?:
Results from trauma or disease in aging.

Addison's

Addison's or Cushing's?:
Loss of gluco- and mineralcorticoids.

Cushing's

Addison's or Cushing's?:
Caused by tumors in adrenal cortex or pituitary.

Cushing's

Addison's or Cushing's?:
Adrenocortical hyperfunction.

21-hydroxylase

Deficiency of this enzyme is the most common steroid hormone disorder.

mineral

Aldosterone is a ______corticoid.

Increased; cortisol; aldosterone; 17; androgen; genitalia

21-Hydroxylase Deficiency

Low GLUCOcorticoids leads to
- ________ in ACTH from the pituitary as part of the normal feedback mechanism.
- ACTH stimulates adrenal cortex to secrete _______, corticosterone, and __________.
- High pregnenolone leads to high progesterone and a __alpha-hydroxyprogesterone, thus high _________ synthesis. If this happens during development this can cause problems with proper development of _________.

Increased; testosterone; cortisol; hypo; aldosterone Na+; water; bone

21- Hydroxylase Deficiency

_______ androgens, because androgens do not have separate feedback mechanism.
Masculinization (androstenedione goes to __________)

Low glucocorticoids because of low ________ leads to ___glycemia.

Low mineralcorticoids because of low _________ leads to loss of __ in the urine and _____ loss. ____ maturation is accelerated.

glucocorticoids; mineralcorticoids

Therapy for 21-Hydroxylase Deficiency:
Administer _________ to eliminate ACTH production. Add _________ to stop salt loss.

True

T or F: Vitamin D is derived from cholesterol.

sterols; hormone

Biological Forms of Vitamin D:
- Group of _____ that have ________-like function.

active; transcription factor; Ca2+; P3+

The ______ form of Vitamin D is 1,25-dihydroxycholecalciferol (1,25 diOH D3). It interacts with DNA via a _________ _______ of target cells and selectively increases or decreases gene transcription depending on the cell type. Most significant is its regulation of plasma levels of ____ and ___.

absorption

Vitamin D is important for maintenance of bone and _______ of Ca and P.

D2; D3; lanosterol; cholesterol; D3

Biological Soruces of Vitamin D:

Ergocalciferol (Vitamin __) from fungi and plankton.
Cholecalciferol (Vitamin __) from animals are precursors of activated vitamin D3

7-dehydrocholesterol (one of the intermediates between _________ and cholesterol) synthesized during _________ biosynthesis is converted to the active __ in the dermis and epidermis of humans exposed to sunlight.

uv; Previtamin; active; liver; 27; Calcitriol

7-dehydrocholesterol, when exposed to __ light in the skin, turns into the cis D3 called ___________ D3. This then turns into the trans D3 which is the _______ form. This is sent to the ______ for storage. It can then be hydroxylated on the 25th carbon by CYP__A1 on its way to the kidney.

In the kidney, we have the source of the sensing of this hormone. The kidney also monitors Ca and phosphate levels, and kidney can convert the 25-cholecalciferol to the active 1,25-dihydroxycholecalciferol (called _________). This will then be transported to the blood to different tissues.

calcitriol

Def.: Steroid hormone secreted by the kidneys when parathyroid hormone is present; stimulates the absorption of calcium and phosphate in the digestive tract.

kidney; liver; activated; activated; calcium; Inhibited; inactive

Vitamin D

1,25-(OH)2D3 hormone is produced primarily in the ______ from 25-(OH)D3 that we got originally from the _____. The enzyme 25-hydroxycholecalciferal 1-hydroxylase does this.

- This reaction is _______ by low phosphate ion.
- This reaction is _______ by Parathyroid Hormone (PTH) that has been released in response to low plasma _________ levels.
- ________ by the product 1,25(OH)2D3.
- 25-(OH)D3 is produced by the liver by hydroxylation. This is the predominant form in the plasma and it is _________.

plasma; intestines; transcription; kidneys; resorption; PTH

Function of Vitamin D

1. Maintain adequate ________ levels of calcium and phosphate. It does this by increasing the uptake of calcium and phosphate from the __________. Vitamin D will actually enter the nucleus of the intestinal cells and increase __________ of the gene encoding a protein that binds calcium.
- We can also increase consumption of Ca and phosphate in the diet.

2. Decrease loss of calcium in the ________.

3. Stimulates ________ of calcium and phosphate form bone when necessary in conjunction with ____. Without bone deposition, we have more fragile bones.

rickets; collagen; osteomalacia

Vitamin D - Deficiency Disease

Demineralization of bone
This causes _______ in children because of the formation of ________ matrix in the bone takes place because of inadequate mineralization. Soft, pliable bones result

This causes _________ in adults. Pre-existing bones lose minerals and become susceptible to fracture.

Northern

Vitamin D deficiency is more common in _________ latitudes because of decreased exposure to UV light.

renal; active

Vitamin D - Deficiency Disease

Renal rickets (renal osteodystrophy) results from chronic _____ failure, where active hormone is synthesized. Treatment is through administration of the _______ form 1,25-diOH D3.

hypo; hyper

Vitamin D - Deficiency Disease

Hypoparathyroidism is a lack of PTH which causes ____calcemia and _____phsophatemia. Treatment is any vitamin D analog and PTH.

most; liver; appetite; Hyper; arteries; kidneys

Toxicity of Vitamin D

- It is the ____ toxic of all vitamins.
- It is stored in the _____ and slowly metabolized.
- High doses can cause loss of ________, nausea, thirst, and stupor. _____calcemia which leads to deposition of calcium in many organs where it doesn't belong, mainly _________ and ________.

Vitamin D

________ _ is used for pest control (mice) instead of Warfarin analogs. Kids, dogs, and other pets can consume the "poison" without serious consequences.

Estradiol

Everybody has testosterone. Women have it as an intermediate in the synthesis of _________.

Addison's

Addison's or Cushings?:
Treat by administering gluco- and mineralcorticoids.

21-hydroxylase deficiency

Most common steroid hormone disorder.

low; winter

Recently, ____ vitamin D levels are being related to the incidence of influenza. This occurs more in the ______ because of exposure to sunlight being reduced.

cancer; Parkinson's

Recent Developments:

There is also a correlation between patients who have low vitamin D levels and have asthma, ________, multiple sclerosis, and __________.

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