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Welcome to my lecturer note

AUTONOMIC AND SYSTEMIC PHARMACOLOGY Sixth Semester

Adrenocorticoids sex
hormones, insulin
Dr. Jibachha Sah
M.V.Sc (Pharmacology)
College of Veterinary Science,
Chitwan, Nepal
Definition

In humans and other animals, the adrenocortical


hormones are hormones produced by the adrenal cortex,
the outer region of the adrenal gland.

These polycyclic steroid hormones have a variety of roles


that are crucial for the body’s response to stress (for
example, the fight-or-flight response), and they also
regulate other functions in the body.
Adrenal Glands
The adrenal glands consist of two layers;
the cortex and medulla.

The adrenal cortex is red to light brown in colour and is


composed of three zones. From the outer to inner, the layers
are;
1. zona glomerulosa
2. zona fasciculata
3. zona reticularis

The adrenal cortex represents 80-90% of the adrenal gland.

The adrenal medulla is primarily involved in the production of catecholamines; epinephrine and norepinephrine. In fetal
life, the adrenal medulla plays a role in the autonomic nervous system.
Functional Anatomy

Cortex: Secretes a variety of steroid hormones derived from cholesterol.

●Zona glomerulosa: Secretes Aldosterone. Concerned with electrolyte and fluid homeostasis.

● Zona Fasciculata: Secretes Glucocorticoids. Controls metabolism of lipid, protein and carbohydrate.

● Zona Reticularis: Produces Sex hormones. Supplements gonadal sex hormone secretion.

● Medulla: Embryologically similar origin to the sympathetic nervous system. Secretes catecholamine
hormones E.g. Adrenaline, noradrenaline.
Pathology of endocrine gland

Endocrine gland there are two main types of pathology:

1. Insufficiency leading to Addisons disease.

2. Excess leading to Cushings disease.


CLASSIFICATION OF SEX HORMONE
Sexual hormones are of two types: proteins and steroids.

1. THE PROTEIN HORMONES

1.1 The gonadotropins

These hormones are produced by different tissues (pituitary and placenta) and their main function is gonadic regulation
(ovaries and testicles). The gonadotropins include:
●FSH ( folliculo-stimulating hormone),
● LH (luteinizing hormone) and
● hCG (human chorionic gonadotropin).
● Prolactin- prolactin is a non-glycosylated protein, function of prolactin is to control breast development and
lactation
Gonadotropin releasing hormone (GnRh)
Mechanism of action of GnRh drug

Gonadotropin receptors are embedded in the surface of the target cell membranes and coupled to the G-protein system.
Signals triggered by binding to the receptor are relayed within the cells by the cyclic AMP second messenger system.

Gonadotropins are released under the control of gonadotropin-releasing hormone (GnRH) from the arcuate nucleus
and preoptic area of the hypothalamus. The gonads — testes and ovaries — are the primary target organs for LH
and FSH.

As a simplified generalization, LH stimulates the Leydig cells of the testes and the theca cells of the ovaries to
produce testosterone (and indirectly estradiol), whereas FSH stimulates the spermatogenic tissue of the testes and
the granulosa cells of ovarian follicles, as well as stimulating production of estrogen by the ovaries.
Diseases
Gonadotropin deficiency due to pituitary disease results in hypogonadism, which can lead to infertility.
2. THE STEROID HORMONES

Oestrogens are of three types:

● oestrone (E1), - his is a weak form of estrogen and the only type found in women after the
menopause.

● oestradiol (E2) - This is the strongest type of estrogen. Estradiol is a steroid produced by the ovaries.
It is thought to contribute to a range of gynecological problems, such as endometriosis, fibroids,
and cancers that occur in females, particularly endometrial cancer.

● oestriol (E3). This the weakest of the estrogens and is a waste product made after the body uses
estradiol. Pregnancy is the only time at which significant amounts of estriol are made. Estriol cannot be
converted to estradiol or estrone.

Far lower levels of estrogen are also present in men.


OESTROGEN HORMONES
Pharmaceutical preparations
Mechanism of action of estrogen hormone drug
Sex hormones further classified as

1.Androgens (Male sex hormone)

2.Estrogens (Female sex hormone)

3.Gestogens(Corpus luteum hormones)

1.Androgens (Male sex hormone)

Androgens are synthesized from cholesterol in the testes and adrenal cortex. Adrenal cortex produce small quantities

of Dehydroepiandrosterone and androstenodione ,which are called WEAK ANDROGENS.

Progestin's are precursor of all androgens


There are 4 naturally occurring in male sex hormone

1. Testosterone (Male sex hormone)

2.Androsterone

3. Epiandrosterone (or) androstenedione

4.Dehydro epiandrosterone (or) DTH


Testosterone

Testosterone belongs to a class of male hormones called androgens, which are sometimes called steroids or
anabolic steroids. In men, testosterone is produced mainly in the testes, with a small amount made in the adrenal
glands. The brain's hypothalamus and pituitary gland control testosterone production
Female sex hormone
1. Estrogen

They play an essential role in the growth and development of female secondary
sexual characteristics, such as breasts, pubic and armpit hair, and the regulation of
the menstrual cycle and reproductive system.

During the menstrual cycle, estrogen produces an environment suitable for the
fertilization, implantation, and nutrition of an early embryo.
Estrogen is responsible for the differences between male and female bodies.
For example, in a female body:

●Estrogen makes the bones smaller and shorter, the pelvis broader, and the shoulders narrower.

●It increases fat storage around the hips and thighs, meaning that the body is more curved and contoured.

●Estrogen helps to slow down the growth of females during puberty and increases sensitivity to insulin. Insulin influences the

amount of body fat and lean muscle a person can develop.

●It influences body hair to become finer and less pronounced while making the hair on a woman's head more permanent.

●Estrogen makes the voice box smaller and the vocal cords shorter, giving females a higher-pitched voice than males.

●Estrogens suppress the activity of the glands in the skin that produce oily substances. This reduces the likelihood of acne in

females.
2.Progesterone
Progesterone, hormone secreted by the female reproductive system that functions mainly to regulate the condition
of the inner lining (endometrium) of the uterus. Progesterone is produced by the ovaries, placenta, and adrenal
glands.

In the ovaries the site of progesterone production is the corpus luteum. Progesterone prepares the wall of the
uterus so that the lining is able to accept a fertilized egg and so that the egg can be implanted and develop.

In the ovaries, progesterone and estrogens are thought responsible for the release of an egg during ovulation.

Many oral contraceptives are composed of a synthetic progestin that inhibits egg growth and release in the
ovaries and thereby prevents fertilization.
Progesterone injection
Mechanism of action of progesterone

Estrogen and progesterone are steroid hormones that play a pivotal role in the regulation of mammalian
reproduction. One primary action of these hormones is to regulate the development and function of the uterus.
These hormones act by regulating the transcription of specific genes in the uterus

Progestin "Generations“

First generation: Norethindrone, norethindrone acetate, and ethynodiol.


Second generation: Desogestrel and norgestrel.
Third generation: Norgestrel and norgestimate.
Fourth generation: Drospirenone.
Insulin

Insulin is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the
main anabolic hormone of the body.It regulates the metabolism of carbohydrates, fats and protein by
promoting the absorption of carbohydrates, especially glucose from the blood into liver, fat and skeletal
muscle cells.
Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells
secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited
The endocrine portion of the pancreas takes the form of many small clusters of cells called islets of Langerhans or, more
simply, islets.

Pancreatic islets house three major cell types, each of which produces a different endocrine product:

●Alpha cells (A cells) secrete the hormone glucagon.


● Beta cells (B cells) produce insulin and are the most abundant of the islet cells.
● Delta cells (D cells) secrete the hormone somatostatin, which is also produced by a number of other
endocrine cells in the body.
Mechanism of action of Insulin
The primary type of Addison’s is a result of dog’s own immune
system destroying the adrenal gland itself.
Addison's Disease in Dogs
Secondary Addison's disease results from a problem, such as a
tumor, in the pituitary gland, which is an important hormonal
regulator located in the brain.

Symptoms may include:


Lethargy
Weakness
Poor appetite
Coloumn Vomiting
Weight loss
chart Depression
Dehydration
Diarrhea
Excessive thirst
Cool to touch
Shaking
Slow heart rate
Addisonian crisis in dogs(life threating situation)
Addison's disease, scientifically known as hypoadrenocorticism, is a disease with serious consequences for dogs,

Clinicopathology:
Anemia and abnormally high levels of potassium and urea in the blood, along with changes in the levels of sodium, chloride,
and calcium in the blood, are symptomatic of Addison’s.

Diagnosis
The definitive test for Addison’s is the adrenocorticotropic hormone (ACTH) stimulation test.

Treatment

Injectable mineralocorticoid (usually DOCP) monthly and a daily steroid (prednisone).


Cushings disease.
Cushing’s disease in dogs develops when their own body overproduces cortisol. Hyperadrenocorticism in dogs generally affects
middle-aged to older animals.

some common symptoms associated with Cushing’s disease in dogs:

●Increased thirst and urination (polydipsia and polyuria, respectively) ● Urinating at night or having accidents
● Increased hunger ● Increased panting
● Pot-bellied abdomen ● Obesity
● Fat pads on the neck and shoulders ● Loss of hair
● Lack of energy ● Muscle weakness
● Infertility ● Darkening of the skin
● Thin skin ● Bruising
● Hard, white scaly patches on the skin, elbows, etc. (associated with the disease calcinosis cutis)
Cushings disease dog Cushings disease in dog.
Causes Cushing's Disease in Dogs
The most common cause of hyperadrenocorticism in dogs is a benign (non-spreading) pituitary tumor. Rarely, pituitary
tumors may be malignant.

Tumors within the adrenal gland (adrenal-dependent hyperadrenocorticism or ADH) are responsible for the other 15
to 20 percent of cases of naturally occurring Cushing’s disease in dogs.

Excessive (high-dose or long-term) administration of corticosteroid medications can also cause hyperadrenocorticism
in dogs.

Diagnosis
The most common test used to diagnose Cushing’s disease in dogs is the low-dose dexamethasone suppression test
(LDDST).

Treatment
If no metastases are seen, the dog is often given a medication (trilostane) for a few months to shrink the tumor,
followed by surgery to remove it.
Diabetes mellitus

Diabetes mellitus is a disease of the pancreas, a small but vital


organ located near the stomach.
Symptoms and Types of Diabetes in Dogs

Early signs
Excessive urination
Excessive thirst
Hunger
Weight loss even with normal appetite
Elevated blood glucose
Glucose in the urine
Later signs
Anorexia – complete loss of appetite
Lethargy and depression
Vomiting
Cataracts
Worsening weight loss
Recurrent infections
Diagnosis of Diabetes in Dogs
Complete blood count, chemical profile, and urinalysis.

Treatment
Look for in case of either hypoglycemia (low levels of glucose) or hyperglycemia (high level of glucose), both of which can
be seen in diabetic dogs.

Keeping a daily and weekly chart of your dog's diet, glucose test results, daily insulin dose,
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