Steroid Biosynthesis Flashcards Preview

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Flashcards in Steroid Biosynthesis Deck (25)
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1
Q

Progesterone and pregnancy

A

supports gestitation (pregnancy) and embryogenesis and is also involved in the maintenence of the menstrual cycle

it regulates the voltage gated Ca channels on the spermatozoa, prepares the uterus for implantation, and causes smooth muscle relaxation

also decreases the maternal immune responses

decrease in progesterone levels precedes menstruation, labor, and lactation

2
Q

Glucocorticoids and infant respiratoory distress syndrome

A

In normal term, infants, a burst of glucocorticoids during delivery alters the lung structure by stimulating the production of surfactant which allows for the air spaces to expand

in preterm neonates, this process is defective leading to infant respiratory distress syndrome (IRDS)
-can be prevented by giving glucocorticoids to expectant mothers

3
Q

Metabolic modulation of steroid effects

A

the response of target tissues to a steroid hormone is determined by furthur metabolism of the hormone

i. e: mineralcorticoid target tissues in the kidneys, colon, and parotid gland contain a receptor that has equal affinities for both mineral and glucocorticoids but normally there is a much higher amount of circulating glucocorticoids so the body will metabolize the cortisol to cortisone by 11B Hydroxysteroid dehydrogenase so that the affinity is much lower
- natural licorice can inhibit this process and lead to hypertension due to increase corticoid and Na/H20 retention

i.e: conversion of testosterone by 5a reductase to DHT makes testosterone mouch more potent for its processes

4
Q

what is finasteride?

A

inhibitor of 5a-reductase that prevents the potentiation of testosterone and has helped with treating benign prostatic hyperplasia, and male pattern baldness

5
Q

what are all steroids synthesized from in the adrenal cortex?

A

Cholesterol

6
Q

what is the function of Desmolase, where is it found, other names, and what stimulates its activity

A

Desmolase is an enzyme that produces pregnenolone from cholesterol, this is the rate limiting and first step to making steroids

Desmolase is also called cytochrome P450scc or CYP11A1

Found in all steroid producing tissues: Adrenal gland, testes, ovaries, and placenta

regulated by adrenocorticotropic hormone (ACTH)
-stimulates the production of pregnenolone

7
Q

what is the Pregnenolone and what is it important for?

A

The most important biochemical intermediate for the steroid making process

Used as a substrate to produce:

  • Progesterone
  • Aldosterone
  • Cortisol
  • Testosterone
  • Estradiol

Pregnenolone contains a double bond to an O at its end

8
Q

Rennin-angiotensin-aldosterone system (RAAS)

A

Controls the blood pressure and fluid balance

kidneys release the enzyme renin into the circulation when low blood volume is sensed

renin will vleave the zymogen angiotensinogen made by the liver that will turn to angiotensin 1 which will be proteolytically processed into the vasoconstrictor angiotensin II in the lung by Angiotensin converting enzyme (ACE)

Angiotensin II also stimulates the release of vasopressin from the pituitary gland and aldosterone from the adrenal gland via the mineralcorticoid cells

these are important in the retention of Na+ and H20 that help raise the blood pressure

9
Q

how do globulins play a role in steroid hormones

A

Steroid hormones are transported in the blood complexed to specific carrier proteins

THe human corticosteroid binding globulin is important in carrying 80-90 percent of thhe plasma glucocorticoid hormones and also progesterone

sex steroids such as testosterone, dihydrotestosterone, and estradiol are transported via the sex steroid hormone binding globulin (SHBG) and to a lesser extent albumin

  • saturated in men
  • patially saturated in females

both globulins are made in the liver

10
Q

Adrenal Hyperplasia

A

Classic and non classic forms of the disease but both are caused by deficiencies in the adrenal enzymes tht are used to synthesized glucocorticoids

increased production from the adrenal gland of both cortisol precursors and androgens

can lead to:

  • sinus infections
  • pulmonary infections
  • orthostatic syncope
  • shortened stature
  • severe acne

women present with hirsutism: excessive body hair

  • General oligomenorrhea: infrequent or light menstruation
  • infertillity
11
Q

how to determine if a paitent has Adrenal hyperplasia

A

Determined using human leukocyte antigen haplotype

demonstation of excess cortisol precursors in amniotic fluid

12
Q

Patient treatment for Adrenal hyperplasia

A

Carefully monitored hormone replacement therapy

  • recognition of the problem
  • timely replacement therapy
  • reduces morbidity and enhances quality of life
13
Q

what are the two enzymes deficient in Adrenal hyperplasia

A

21 hydroxylase (Cyp21A2)

  • cant turn progesterone to deoxycorticosterone to make aldosterone
  • cant turn 17hydroxy progesterone to 11-deoxycortisol to make cortisol

11-B hydroxylase (CYP11B1(

  • cant turn deoxycorticosterone to corticosterone to make aldosterone
  • cant turn 11-deoxycortisol to cortisol
14
Q

Primary Aldosteronism

A

Adrenal cortex (zona glomerulosa)

  • promotes the retention of Na+ amnd H20 in the kidneys
  • promotes excretion of H+ and K+
15
Q

Conn syndrome

A

Endocrine disorder of the adrenal glands

  • excessive secretion of aldosterone
  • retention of sodium
  • loss of potassium
  • high blood pressure (hypertension)
16
Q

What steroids can activate the MR?

A

Mineralcorticoid reeptor

  • Aldosterone
  • 11-deoxycorticosterone
  • testosterone
  • hydrocorticosone (cortisol)
  • cortisone

in order of most efficacious to least
all these lead to increase Na retention

17
Q

how does an 11B hydroxylase deficiency lead to hypertension

A

even though this is decreasing the amount of aldosterone production and cortisol production, there is an increase in levels of 11-deoxycorticosterone and 11-deoxycortisol

11-deoxycorticosterone has a relatively high affinity for Mineralcorticoid receptor that will produce the retention of Na+ and then the hypertension that follows

18
Q

Cortisol suppression of the

A

Glucocorticoids such as cortisol cause immunosuppressive behaviors by inhibiting both cellular and humoral immune responses

induce the production of i-kBa inhibitory protein that helps sequester the transcription factor nuclear factor kappa B which is necessary for the synthesis of many cytokines such as IL-2 (important for T-cell proliferation)

cortisol also promotes T cell apoptosis and decreased IL-2 and its receptor will lead to an inhibition of clonal expansion of B lymphocytes as well

19
Q

what is the HPA axis for cortisol

A

Hypothalamus releases CRH (Corticotropin releasing hormone) this acts on the anterior pituitary that releases ACTH (Adrenocorticotropic hormone) on adrenal cortex which releases Cortisol

20
Q

what is the regulation of Cortisol synthesis

A

when the cortisol levels fall the hypothalamus produces CRH which stimulates the release of ACTH from the anterior pituitary which then acts on the adrenal gland to release cortisol

cortisol levels will serve as a negative feedback loop to CRH and ACTH

21
Q

How does ACTH act on the adrenal gland? and its receptor?

A

acts on the adrenal Cortex specifically the zona Fasciculata that stimulates the secretion of glucocorticoid steroid hormones

acts by binding to cell surface ACTH receptors which is a 7 membrane spanning GPCR which is located primarily on adrenocortical cells of the adrenal cortex

22
Q

difference between the ACTH activation in a normal cell a tumor cell

A

normal cell: activation of adenylcyclase to produce cAMP that activates PKA that activates CREB to produce cortisol

Tumor cell: constitutively active pKA promoting CREB and cell proliferation

23
Q

Influences ACTH has on steroid hormone secretion

A

in minutes: stimulates desmolase to promote the production of pregnenolone

in hours:

  • stimulation of lipoprotein uptake in cortical cells
  • increases bioavailability of cholesterol
  • stimulation of transcription genes coding for steroidogenic enzymes
  • p450scc (desmolase)
  • steroid 11B-hydroxylase
  • associated electron transfer proteins
24
Q

what 17,20 lyase important for? what happens if there are mutations associated with this enzyme

A

also known as CYP17A1

key enzyme in the steroidogenic pathway that produces progestins, mineralcorticoids, glucocorticoids, androgens, and estrogens

  • Dehydroepiandrosterone (DHEA)
  • Androstenedione

mutations in the 17a-hydroxylase/17,20 lyase lead to pseudo-hermaphroditism and adrenal hyperplasia
as well as 46,XY disorders of sex development

25
Q

how is Cholecalciferol obtained in the body? and how is it converted to its active form in the body

A

Cholecalciferol (vitamin D3) is obtained in two ways:

Through the diet of eating ergocalciferol (vitamin D2) that is absorbed in the intestine from dietary sources
-converted from 7-dehydrocholesterol in the skin via UV radiation

In the kidney 1,25 Dihydroxycholecalciferol (calcitrol to active form vitamin D) is synthesized by 1-a hydroxylase

  • done via PTH and low Phosphate
  • inhibited by calcitrol (negative feedback loop)

25-hydroxycholecalciferol is found exclusively in the liver via the conversion by 25-hydroxylase from cholecalciferol