STEROIDS

USC DEPARTMENT OF PHARMACY

 Synthesis of Steroid Hormones

Overview of Steroids
Peptide Hormone vs. Steroid Hormone Synthesis
The Role of Cholesterol
Adrenal Steroids
Steroids from the Testis
Ovarian Steroids
Cortisol
 Steroid Hormones
• Steroid hormones: produced in the adrenal
cortex, testis, ovary, and some peripheral tissues
(adipose tissue, the brain!)
• All steroid hormones share a typical (but not
identical) ring structure.
 Steroid hormones
All steroid hormones are derived from cholesterol and differ
only in the ring structure and side chains attached to it.
All steroid hormones are lipid soluble
 Types of steroid hormones
• Glucocorticoids; cortisol is the major representative in most
mammals
• Mineralocorticoids; aldosterone being most prominent
• Androgens such as testosterone
• Estrogens, including estradiol and estrone
• Progestogens (also known a progestins) such as progesterone
 Steroid hormones
• Are not packaged, but synthesized and immediately released
• Are all derived from the same parent compound: Cholesterol
• Enzymes which produce steroid hormones from cholesterol are located
in mitochondria and smooth ER
• Steroids are lipid soluble and thus are freely permeable to membranes
so are not stored in cells
 Steroid hormones
• Steroid hormones are not water soluble so have to be carried in the
blood complexed to specific binding globulins.
• Corticosteroid binding globulin carries cortisol
• Sex steroid binding globulin carries testosterone and estradiol
• In some cases a steroid is secreted by one cell and is converted to the
active steroid by the target cell: an example is androgen which secreted
by the gonad and converted into estrogen in the brain
Steroids can be transformed to active steroid in
target cell
 Steroid Hormones
• Steroid hormones are nonpolar (no net charge), and
can thus diffuse across lipid membranes (such as the
plasma membrane). They leave cells shortly after
synthesis.
phospholipid

Polar substances are water soluble (dissolve in water),

nonpolar substances are lipid soluble.
 Functions of Steroid Hormones

• Steroid hormones play important roles in:

- carbohydrate regulation (glucocorticoids)
- mineral balance (mineralocorticoids)
- reproductive functions (gonadal steroids)

• Steroids also play roles in inflammatory

responses, stress responses, bone metabolism,
cardiovascular fitness, behavior, cognition, and
mood.
 How does the synthesis of steroids differ
from that of peptide hormones?
• While peptide hormones are encoded by specific genes, steroid
hormones are synthesized from the enzymatic modification of
cholesterol.
• Thus, there is no gene which encodes aldosterone, for example.
• As a result:
- There are far fewer different types of steroid hormones
than peptide hormones.
- Steroid structures are the same from species to species
- The regulation of steroidogenesis involves control of the
enzymes which modify cholesterol into the steroid hormone of
interest.
 The Role of Cholesterol in Steroid Synthesis

• The first enzymatic step in the production of ANY

steroid hormone begins with enzymatic
modification of cholesterol
 Sources of Cholesterol for Steroid Synthesis
• Cholesterol can be made within the cell from acetyl CoA
(de novo synthesis).
• This is a multistep process, involving many enzymatic
reactions.
• A key rate-limiting enzyme is HMG-CoA reductase.
• There is negative feedback regulation of HMG-CoA
reductase activity by cholesterol, so that high
intracellular cholesterol inhibits de novo synthesis.
HMG-CoA reductase
acetyl CoA HMG-CoA mevalonate cholesterol
 Sources of Cholesterol for Steroid Synthesis

• Cholesterol is also taken up by the cell in the form of

low density lipoprotein (LDL).
- LDL is a complex composed of cholesterol,
phospholipids, triglycerides, and proteins (proteins
and phospholipids make LDL soluble in blood).
- LDL is taken into cells via LDL receptors, and broken
down into esterified cholesterol, and then free
cholesterol:

LDL esterified cholesterol free cholesterol

LDL
receptor
 Source of Cholesterol for Steroid Synthesis
• The amount of free cholesterol in the cell is
maintained relatively constant:

cellular synthesis
of cholesterol free
cholesterol steroid
level synthesis

esterified cholesterol level

LDL
 Cellular Localization of Cholesterol
Metabolism for Steroid Production
• The first enzymatic step in steroid synthesis is the
conversion of cholesterol into pregnenolone.
• The enzyme that catalyzes this reaction is located
in the inner mitochondrial membrane.
 Steroidogenic Enzymes
Common name "Old" name Current name

Side-chain cleavage enzyme; P450SCC CYP11A1

desmolase

3 beta-hydroxysteroid 3 beta-HSD 3 beta-HSD

dehydrogenase
17 alpha-hydroxylase/17,20 lyase P450C17 CYP17

21-hydroxylase P450C21 CYP21A2

11 beta-hydroxylase P450C11 CYP11B1

Aldosterone synthase P450C11AS CYP11B2

Aromatase P450aro CYP19

 Steroid hormone synthesis
All steroid hormones are derived from cholesterol.
A series of enzymatic steps in the mitochondria
and ER of steroidogenic tissues convert
cholesterol into all of the other steroid hormones
and intermediates.
The rate-limiting step in this process is the
transport of free cholesterol from the cytoplasm
into mitochondria. This step is carried out by the
Steroidogenic Acute Regulatory Protein (StAR)
 Steroid hormone synthesis
•The cholesterol precursor comes from cholesterol
synthesized within the cell from acetate, from
cholesterol ester stores in intracellular lipid
droplets or from uptake of cholesterol-containing
low density lipoproteins.
•Lipoproteins taken up from plasma are most
important when steroidogenic cells are chronically
stimulated.
 Extracellular
lipoprotein LH
Cholesterol
acetate pool
ATP

cholesterol cAMP
PKA+

Pregnenolone
3bHSD
Progesterone
P450c17
Androstenedione
17bHSD
TESTOSTERONE
 Functions of Hormones
Derived from Cholesterol

Product
Progesterone
Glucocorticoids (cortisol)
(produced in adrenal cortex)
(catabolic steroid)
Mineralocorticoids
(aldosterone) (produced in
adrenal glands)
Functions
prepares uterus lining for
implantation of ovum
promote gluconeogenesis;
favor breakdown of fat and
protein (fuel mobilization);
anti-inflammatory
maintains blood volume and
blood pressure by increasing
sodium reabsorption by kidney
 Functions of Hormones
Derived from Cholesterol

Product Functions
Androgens (strongest = testosterone) development of male
(produced in testes primarily but weak secondary sex
androgens in adrenal cortex) (anabolic characteristics; prevents
steroid) bone resorption
Estrogen development of female
(produced in ovaries primarily but also secondary sex
in adipose cells of males and females) characteristics; prevents
bone resorption
Vitamin D (not a steroid hormone) intestinal calcium
(produced in the skin in response to absorption; promotes
UV light and processed to active form bone formation; prevents
in kidney) phosphate loss by
kidneys
 activated to
turn
Cholesterolon pathways Pregnenolon Progesterone
e

Progesterone 11-Deoxy- Aldosterone

cortisone
21-hydroxylase

Progesterone 11-Deoxy- Cortisol

21-hydroxylase cortisol

General pathways for the synthesis of aldosterone and

cortisol in the adrenal cortex
Pregnenolone DHEA Androstenedion
Androstenedione
e
“Andro”

Pathway for formation of androgens in the adrenal cortex.

Beware of the hype about taking DHEA
Cortisol made in same cells as androstenedione
 Cholesterol Pregnenolone Progesterone

Progesterone Androstenedione Testosterone

(pathway ends
here in testes)

Estrone
(produced in both male
and female adipose cells) Estradiol
(pathway continues
to here in ovaries)
In obese men, overproduction of estrogen in fat cells
can cause gynecomastia = excessive male breast
development
Pathways for the synthesis of testosterone (testes) and the
estrogens estradiol (ovaries) and estrone (adipose cells)
 Liver OHase =
Diet OH
hydroxylase
25-OHase

HO
HO
Vitamin D3 25(OH) D3
Kidney Specific receptors in
UV from 1-OHase intestine, bone, kidney
Skin
sunlight
Ca:
OH Intestinal absorption
Renal reabsorption

HO 7 PO4:
Intestinal absorption
Provitamin D3 HO OH Renal reabsorption
(7-dehydrocholesterol: 1,25(OH)2 D3
Intermediate in cholesterol (active hormone form)
synthesis)

Photobiosynthesis of vitamin D3 and its metabolism

 1,25-Dihydroxy Vitamin D3
1,25-dihydroxy Vitamin D3 is also derived from cholesterol and
is lipid soluble
Not really a “vitamin” as it can be synthesized de novo
Acts as a true hormone
 Adrenal Cortex: Steroid Hormone
Production

• Aldosterone, sex hormones, cortisol

• Synthesized from cholesterol–steroid ring
Adrenal Cortex: Steroid Hormone Production
 Transport of Cholesterol
• Cholesterol is lipid soluble, and mostly located
associated with the external mitochondrial membrane.
• The conversion of cholesterol to steroids occurs in the
internal mitochondrial membrane.
• Now, to see if you have been paying attention…
• How does cholesterol get from the external membrane
to the internal membrane?
• Answer: Steroidogenic acute regulatory protein (StAR),
which transports cholesterol into the mitochondria,
moving it from the outer membrane to the inner
membrane.
 Adrenal Steroids

• The adrenal glands are located immediately

superior to the kidneys.
• There are three classes of adrenal steroids:
- mineralocorticoids,
- glucocorticoids, and
- androgens
 Organization of the Adrenal Gland

There is an adrenal cortex and adrenal medulla.

Steroids are made in three zones of the adrenal cortex:

mineralocorticoids: zona glomerulosa
glucocorticoids: zona fasciculata
androgens: zona reticularis

(What’s made in the adrenal medulla??)

 Adrenal Steroidogenesis
• The first enzymatic step is the conversion of cholesterol to
pregnenolone, which occurs in the mitochondria.
• This reaction is carried out by the enzyme, cytochrome P450
side-chain cleavage (P450scc; also called desmolase, or
CYP11A1).
• This is a rate limiting, nonreversible step in the initiation of
steroid biosynthesis.
• This step occurs in adrenal, ovary, and testis.
 Adrenal Steroidogenesis
• Next, pregnenolone can be converted into three
different pathways, depending upon whether you
want to make mineralcorticoids, glucocorticoids, or
androgens:
17a-hydroxylase lyase
pregnenolone 17a-hydroxypregnenolone dehydroepiandrosterone
3b-hydroxysteroid dehydrogenase
progesterone androstenedione
21-hydroxylase

11b-hydroxylase

18 hydroxylase/oxidase glucocorticoids
mineralocorticoids (cortisol)
(aldosterone)
 Adrenal Steroidogenesis
What determines which pathway is taken?
• Each step of the pathway is regulated by a specific
enzyme.
• Different zones of the adrenal cortex have different
relative activities of enzymes, resulting in different
chemical reactions taking place.
• These enzymes are located in the smooth ER.

In the adrenal, you do NOT have to learn the names of these

enzymes. You DO have to understand what hormones are
produced, where they are produced, and why they are
produced there.
 Production of Steroids in the Testis

• The main steroid produced in the male is

testosterone, from the testis. In addition, the
testis makes some androstenedione,
dihydrotestosterone, and estradiol.
• In the male, there is peripheral conversion of
testosterone to dihydrotestosterone (in androgen
target tissues, like muscle) and estradiol (mostly
in adipose tissue).
 Organization of the Testis
• The testis is organized into two main parts:
- seminiferous tubules: production of sperm cells,
location of Sertoli cells (stay tuned...)
- interstitial tissue: outside of the seminiferous
tubules; the steroidogenic cell is the Leydig cell
 Function of Leydig Cells

• Leydig cells: respond to luteinizing hormone (LH)

with steroid production (primarily testosterone).

• Leydig cells are unusual in that they rely on de

novo synthesis of cholesterol more than other
cells (50%). Thus, only about 50% of cholesterol
used in steroid production is obtained from LDL.
 Pathway of Testosterone Production
in the Testis
• The production of androgens from cholesterol is
identical to that in the adrenal, except that it
continues from androstenedione to testosterone.

17b-hydroxysteroid
oxidoreductase
androstenedione testosterone
 Testosterone Metabolism

• Testosterone can then be converted (mostly in

peripheral tissues) to:
- DHT (dihydrotestosterone) by 5a-reductase, or to
-estradiol (E2) by cytochrome P450 aromatase
 Ovarian Steroidogenesis

• The ovary produces estrogens (primarily

estradiol), progesterone, and androgens.
• It relies largely on LDL as a source of cholesterol
for steroid synthesis (compare with testis).
• Ovarian steroids are secreted primarily from
ovarian follicles and corpora lutea.
 Ovarian Follicle

• The follicle is the basic functional unit of the ovary.

• It is composed of an oocyte, granulosa cells, and theca
cells.

• When the follicle ruptures, it becomes a corpus luteum.

 The Puzzle of Estrogen Production in the
Ovary
• In the ovary, estradiol is formed from the conversion
of testosterone into estradiol by the enzyme
cytochrome P450 aromatase. This occurs in
granulosa cells.
• However, granulosa cells do not have the enzyme
17a-hydroxylase/lyase, and thus cannot convert
progesterone into androgens.
• Where do the androgens required for estrogen
production in granulosa cells come from?
 The Two-Cell Theory of Estrogen Production
in the Ovary
• Numerous studies have now shown that the
androgens required for aromatization come from the
neighboring theca cells:
LH FSH
LH receptor

cholesterol

estradiol

aromatase
androgens androgens

theca cell granulosa cell

 Other Steroid Production in the Ovary

• After ovulation, the corpus luteum produces progesterone and estradiol, to

support the uterine endometrium during pregnancy.
• Progesterone is also produced from theca cells and granulosa cells.
 Regulation of Ovarian Steroidogenesis
• The rate of estradiol production from follicles varies greatly during the
menstrual cycle.
• Estradiol production is regulated by the effects of FSH on P450 aromatase.
• Similarly, LH and FSH influence the expression of P450scc in granulosa cells.
This increases production of which gonadal steroid?

P450scc 3b-HSD
cholesterol pregnenolone progesterone
Cortisol Effects: Body Responses to Stress

• Permissive effect on glucagon

• Memory, learning and mood
• Gluconeogenesis
• Skeletal muscle breakdown
• Lipolysis, calcium balance
• Immune depression
• Circadian rhythms
Cortisol Effects: Body Responses to Stress

Figure 23-4: Circadian rhythm of cortisol secretion

 Control of Cortisol Secretion: Feedback Loops

• External stimuli
• Hypothalamic
• Anterior Pituitary
• Adrenal cortex
• Tissues

Figure 23-3: The control pathway for cortisol

Cortisol: Role in Diseases and Medication

• Use as immunosuppressant
– Hyperimmune reactions (bee stings)
– Serious side effects
• Hypercortisolism (Cushing's syndrome)
– Tumors (pituitary or adrenal)
– Iatrogenic (physician caused)
• Hypocortisolism (Addison's disease)
 Steroid Hormones: Characteristics

• Are made from cholesterol, are lipophilic & can

enter target cell
• Are immediately released from cell after
synthesis
• Interact with cytoplasmic or nuclear receptors
• Activate DNA for protein synthesis
• Are slower acting and have longer half-life than
peptide hormones
• Examples: cortisol, estrogen & testosterone
Steroid Hormones: Review the Structure
Steroid Hormones: Molecular Action
 Steroid Hormone Receptors
• Regulate tissue specific gene expression
1. Estrogen receptors
– ER alpha and beta (ovaries and prostate)
– Found in uterus, vagina, ovaries, hypothalamus, endothelia cells
2. Progesterone receptors
– PR A (inhibitor of AR, ER, GR, MR, and PRb (mediates stimulatory action of
progesterone)
3. Androgen, Glucocorticoid, Mineralocorticoid receptors
– Present only in single form
– Mutant forms are associated with disease states
 Estrogens
• Endogenous forms: estradiol, estrone, estriol
• Biologic activities: role in menstrual cycle, development of secondary
sex characteristics in women.
– Proliferation of breast ductile system
– Development of lipid and other tissues (breast shape)
– Fluid retention in breasts (menstruation)
– Growth and development of vagina, uterus, and fallopian tubes
– Sexual arousal (in combination with other hormones)
– Body contour
– Pigmentation of nipples and vagina
 Estrogens
• Structural classes:
– Steroidal estrogens (conjugated and esterified estrogen)
– Diethylstilbestrol
– Phytoestrogen
• Therapeutic uses:
– Birth control
– Hormone replacement therapy
– Treatment of estrogen from ovarian failure or often after oophorectomy
– Treatment of advanced, inoperable breast cancer in men and postmenopausal
women and of advanced, inoperable prostate cancer in men
 Estrogen Products
• Estradiol, USP
– 17-alpha-ethinyl estradiol
• Most commonly used in contraception
• 15-20 more water soluble
• Estradiol 3-acetate (oral, vaginal ring)
• Estradiol 17-valerate
• Estradiol 17-cypionate
• Estriol, USP
– Used for hormone replacement therapy (HRT)
 Estrogen Products
• Estrone, USP
– Less active than estradiol
– Originally obtained from pregnant mares
• Piperazine Estrone sulfate, USP (better oral availability)
• Conjugated Estrogens, USP (HRT)
• Synthetic Conjugated Estrogens
• Esterified Estrogens
 Selective Estrogen Receptor Modulators
(SERM) and Antiestrogens
• Antagonists of ER are of great interest in the treatment of
estrogen dependent breast cancers.
• 60% of breast cancers have shown to have ER and most are
responsive to estrogen blockade.
• Used in the management of breast cancer, ovulation stimulant,
and prevention and treatment of osteoporosis.
 Selective Estrogen Receptor Modulators
(SERM) and Antiestrogens
• Tamoxifen citrate, USP
– Used to treat early and advanced breast carcinoma in
postmenopausal women, metastatic breast cancer (men and women)
and reduce incidence of breast cancer in women.
• Toremifene citrate, USP
– Uses are similar with tamoxifen
– Lower incidence of endometrial cancer than tamoxifen
 Selective Estrogen Receptor Modulators
(SERM) and Antiestrogens
• Raloxifene, USP
– Used for prevention and treatment of osteoporosis in
postmenopausal women
• Bazedoxifene, USP
– Used for prevention and treatment of osteoporosis in
postmenopausal women
• Clomiphene, USP
– Ovulation stimulant
– “increase the odds of a successful pregnancy”
 Aromatase Inhibitors
• Aromatase, a CYP 450 enzyme catalyzing conversion of
androstenedione to estrone and testosterone to estradiol.
• Aromatase reduction is unique to estrogen biosynthesis. Thus,
inhibitors result to estrogen biosynthesis blockade.
• Used in the treatment of estrogen dependent breast cancer.
 Aromatase Inhibitors
• Anastrozole, USP
– First line treatment of postmenopausal women with advanced or
metastatic breast cancer.
• Letrozole, USP
– Identical indications with anastrozole
• Exemestane, USP
– First steroid-based aromatase inhibitor
 Aromatase Inhibitors
• Aminoglutethimide, USP
– Inhibitor of P450scc, weak inhibitor aromatase
– Used of the treatment of Cushing syndrome and estrogen dependent
breast cancer.
• Testolactone, USP
 Progestins
• Progesterone is produced in the ovaries, testes, and adrenal
glands.
– In uterus, it promotes development of the secretory endometrium
– It thickens cervical secretion, decreasing penetration of sperm.
– Maintenance of pregnancy by suppressing menstruation and
decreasing uterine contraction
– Thermogenic action (slight increase) during menstrual cycle.
 Therapeutic Uses of Progestins
• Birth control
• Reduction of the risks of endometrial cancer
• Primary and secondary amenorrhea and functional uterine
bleeding caused by insufficient progesterone production or
Estrogen-Progesterone imbalance
 Progestins
• Progesterone, USP
– Ineffective orally, thus given IM or as vaginal gel
– Light sensitive
• Hydroxyprogesterone caproate, USP
– Given IM
– Prevent pre-term labor
• Medroxyprogesterone acetate, USP
– Used for many menstrual disorder, palliative treatment of advanced endometrial,
breast, and renal carcinoma, and birth contro;
– Depo-provera
 Progestins
• Megestrol acetate, USP
– Palliative treatment for endometrial or breast carcinoma
• Nomegestrol acetate, USP
– Oral contraceptive
• Norethindrone, USP and Norethynodrel, USP
– Oral contraceptive
• Ethynodiol diacetate, USP
 Progestins
• Norgestrel, USP and Levonorgestrel, USP
– used in oral and implant contraceptives
• Desogestrel, USP
• Norgestimate, USP
• Norelgestromin, USP
• Etonogestrel, USP
• Drospirenone USP
• Trimegestrone
 Progesterone Receptor Antagonists and
Selective Progesterone Receptor Modulator
• Mifepristone
– Abortive (first 49 days)
– Causes decrease in progesterone secretion, leads to increase PG
levels stimulating uterine contractions
– Used in conjunction with Misoprostol (PGE2)
 Androgens
• Referred to as “male” sex hormone
• Predominantly produced in male than females
• Activities:
– Androgenic: male sex characteristics
– Anabolic: muscle building
 Biological Activities of Androgens
• Induction of development of the prostate, penis, and related
sexual tissues.
• At puberty, testosterone causes increase in facial and body
hair, deepening of the voice, increased protein anabolic activity
and muscle mass, rapid growth of long bones, and loss of some
subcutaneous fat.
• Onset of spermatogenesis
• Sexual organs increase in size
 Biological Activities of Androgens
• Androgens play important roles in male psychology and
behavior
• In women, testosterone plays a role in libido, mood, bone
density, muscle mass and strength.
 Anabolic Androgenic Steroid Products
• For androgen replacement therapy in men
• Contraindications:
– Prostate cancer
– Heart, kidney, liver disease
– Pregnancy
– Oral anticoagulants (potentiation)
– Virilization in women
 Anabolic Androgenic Steroid Products
• Testosterone (cypionate, eneanthate, propionate,
undecanoate), USP
– For male hypogonadism
– Not feasible as oral route, thus, available as TDDS, implant, IM, gel,
buccal
• Fluoxymesterone, USP
– 5-10 more potent than testosterone
• Methyltestosterone
– Orally active
 Anabolic Androgenic Steroid Products
• Oxymetholone, USP
– For various forms of anemia
• Oxandrolone, USP
– Indicated for weight gain, relieve bone pain (osteoporosis), alcoholic
hepatitis, and HIV wasting syndrome
• Nandrolone decanoate, USP
– Used in management of certain anemia inferior in comparison with
erythropoietin)
 Endometriosis
• Danazol, USP
– Increases free testosterone
– Alters endometrial tissue becoming inactive and atrophic
– Used in the treatment of hereditary angioedema and fibrocystic breast disease
– Androgen Receptor (AR) antagonists
– Used in treating hyperandrogenism (hirsutism, acute acne, premature baldness)
or androgen-stimulated cancers (prostate cancer)
– Ideal antiandrogen: nontoxic, highly active, and devoid of any hormonal activity.
 Antiandrogen Products
• Flutamide, USP
– Indicated for prostate cancer
– SE: hepatotoxic, diarrhea
• Bicalutamide, USP
– Indicated for prostate cancer
– More potent than flutamide and less toxic
– Once a day dosing, preferred choice when initiating therapy
• Nilutamide, USP
– Used as adjunct in castration for the treatment of metastatic prostate cancer
– SE: visual distrubances, alcohol intolerance, and allergic pneumonitis
 5-alpha Reductase Inhibitors
• If testosterone is acted on by 5-alpha reductase (Type II), 5-
alpha dihydrotestosterone (DHT), an androgen maintaining
prostate function is produced.
• However, other studies suggest that both enzyme isoforms
play a role in the progression of prostate cancer. Hence, dual
5-alpha reductase inhibitors have been developed.
• DHT plays a major role in the pathogenesis of benign prostatic
hyperplasia
 5-alpha Reductase Inhibitors
• Finasteride
– Selective inhibitor of Type II 5-alpha reductase
• Dutasteride
– Dual 5-alpha reductase inhibitor
– Also for the treatment of male pattern baldness
– Both agents should be avoided by pregnant women as it could cause
abnormalities in a male baby’s external genitalia
• Saw palmetto (Serenoa repens)
-used to treat benign prostatic hyperplasia (BPH)
 Adrenal Cortex Hormones
• Produced in the adrenal glands
• Mineralocorticoids
– Maintains constant electrolyte balance and blood volume
– Aldosterone promotes sodium reabsorption causing increase in blood
volume while promoting potassium excretion
 Adrenal Cortex Hormones
• Glucocorticoids
– Carbohydrate, protein, and lipid metabolism
– It regulates growth hormone gene expression
– Anti-inflammatory and immunosuppressive actions
– Stimulates gluconeogenesis
• Both classes exhibit varying salt retention properties
Therapeutic Uses of Adrenal Cortex Hormones
• Primarily used for its glucocorticoid effects
(immunosuppression, anti-inflammatory, anti-allergy, Cushing
syndrome, rheumatoid arthritis, disseminated lupus
erythematosus, adjunct in chronic lymphocytopenic leukemia,
and congenital adrenal hyperplasia).
• MCs are used for Addison’s disease (chronic adrenocortical
insufficiency).
Therapeutic Uses of Adrenal Cortex Hormones
• Contrindications:
– Peptic ulcer (steroids may cause hemorrhage)
– Heart disease
– Infections (GC’ immunosuppression)
– Psychoses (behavioral disturbance may occur during therapy)
– Diabetes (GC increase glucose production)
– Glaucoma (induced by steroids)
– Osteoporosis (induce metabolism of calcium)
– Herpes simplex involving cornea
 Mineralocorticoid Products
• Aldosterone is too expensive to produce commercially;
therefore, other semisynthetic analogs are used
• Fludrocortisone acetate, USP
– Used for the treatment of Addison’s disease
 Glucocorticoid Products
• Patient on long-term therapy must have the dose reduced
gradually
• (see book)
 Mineralocorticoid Receptor Antagonists
• Also known as “Aldosterone antagonists”
• Antagonism of the MR can have profound effects on the renin-
angiotensin system
• Spironolactone, USP
– Used as a diuretic
• Eplerenone, USP
– Used in the treatment of hypertension
 Neurosteroids
• Neurosteroids
– Synthesized in the brain (from cholesterol or steroid hormones)
– It includes pregnenolone, progesterone, DHEA
– Hypothesized to have neuroprotective and anxiolytic effects, and may
paly roles in modulating seizures
• Neuroactive steroids
– Synthesized in other steroidogenic tissues