1. Dr. Areej M. Al-Taweel Pharmacognosy Department
PHG Hormones
Dr. Areej M. Al-Taweel
Pharmacognosy Department

2. Hormones Definition: Natural secretion of the endocrine system
that exert important functional effects upon other tissues
in minute concentrations.
Endocrine system: Composed of group of glands
called “Endocrine glands”.
Endocrine glands: Glands that pour their secretion
directly to the blood.

3. Components of the Endocrine System

4. Hypothalamus: Located at the base of the brain
Hypothalamus: Located at the base of the brain. It secretes Releasing and Inhibiting hormones that target the Anterior pituitary gland and control its secretions.

5. Hypothalamic hormones include:
TRH: Thyrotrophin-releasing hormone
CRH: Corticotrophin- releasing hormone
GnRH: Gonadotrophin- releasing hormone
PIH: Prolactin-inhibiting hormone probably dopamine.
PRH: Prolactin-releasing hormone.
GHIH: Growth hormone- inhibiting hormone
(Somatostatin)
GHRH: Growth hormone-releasing-hormone.
These hormones are carried to the anterior pituitary by the
hypothalamo-hypophyseal portal system.
Secretions of the anterior pituitary are also regulated by the
feedback (usually negative feedback) exerted by target gland
hormones.

6. Pituitary gland:
* The Hypothalamus is directly above the pituitary gland is connected to the posterior pituitary (neurohypophysis) by the pituitary stalk. * The Hypothalamus is connected with anterior pituitary (adenohypophysis) through the hypophyseal portal system. * The pituitary gland is the master gland regulating the function of several other endocrine glands.
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland. The anterior pituitary regulates several physiological processes including stress, growth, and reproduction.
Its regulatory functions are achieved through the secretion of various peptide hormones that act on target organs including the adrenal gland, liver, bone, thyroid gland, and gonads. The anterior pituitary itself is regulated by the hypothalamus and by negative feedback from these target organs
The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary gland..

7. Anterior Pituitary gland: Secretes hormones that control the secretion of the other endocrine organs such as adrenal and thyroid glands.
Thyroid Adrenal Gonads

8. A. Anterior pituitary hormones are Classified into:
Somatotropic Hormones:
1- Growth Hormone (GH).
2- Prolactin (Prl).
3- Placental Lactogen (PL).
Glycoprotein Hormones:
1- Luteinizing Hormone (LH).
2- Follicle-Stimulating Hormone (FSH).
3- Chrionic Gonadotropin (CG).
4- Thyroid-Stimulating Hormone (TSH).
Pro-Opiomelanocortin (POMC) derived Hormones:
1- Corticotrophin: ACTH.
2- Melanocyte-Stimulating Hormones: a-MSH, b-MSH.
3- Lipotropins: b-LPH, -LPH
ACTH and LPH a glycopeptide derived from the amino terminus of proopiomelanocortin (76 amino acid)with 30 amino acid residue

9. B. The posterior pituitary releases:
- Antidiuretic hormone (also called vasopressin)
- Oxytocin.
* Both of which are produced in
the hypothalamus and transported
to the posterior pituitary by the
hypothalamo-hypophyseal nerve tract.

10. Adrenal gland
The adrenal glands are located on the superior surface of the kidney.
Adrenal Cortex
Adrenal medulla

11. The gonads secrete sex steroid hormones:
A. Leydig cells in the interstitial tissue of the testes secrete testosterone and other androgens.
B. Granulosa cells of the ovarian follicles secrete estrogen.
C. The corpus luteum of the ovaries secretes progesterone,
as well as estrogen.
VI. The placenta secretes estrogen, progesterone, and a variety of polypeptide hormones that have actions similar to some anterior pituitary hormones.

12. Pancreas:
The endocrine part of the pancreases, namely the islets of Langerhans, contains:
- Alpha cells that secrete Glucagon
- Beta cells that secrete Insulin

13. Thyroid and Parathyroid glands:
- It located at the base of the neck.
- It is a highly vascular bilobed structure.
- The main hormones secreted by the thyroid gland are:
■ Iodinated derivatives of Thyroxine (T4) and Triiodothyronin (T3).
■ Calcitonin.
* Parathyroid glands:
- Small structures embedded within the thyroid gland.
- They secrete a parathyroid hormone (PTH) which promotes
a rise in blood calcium levels.

14. Hypothalamic releasing/inhibiting hormones alter release of anterior pituitary's, which act on other endocrine or target

15. Chemical Classification of Hormones
A- Steroidal Hormones:
1- Adrenocorticoids:
Glucocorticoids e.g. Hydrocortisone.
Mineralocorticoids e.g. Aldosterone.
2- Sex Hormones:
Female sex hormones e.g. Estrogens and Progestins
Male sex hormones e.g. Androgens.

16. B- Amino acids derived hormones:
1- Hormones derived from single amino acid e.g. Thyroxin.
2- Peptide hormones:
i- Only amino acids:
*Anterior Pituitary hormones:
- Prolactin Growth Hormone Placental lactogen.
* Corticotropins: Adrenocorticotropic hormone ACTH.
* Insulin
* Parathyroid hormone and Calcitonin.
ii- Glycoproteins (Amino acids and sugars):
*Anterior Pituitary Hormones:
- Leuteinizing hormone (LH) Follicle Stimulating hormone (FSH)
- Chorionic Gonadotropin (CG) -Thyroid Stimulating hormone (TSH).

17. Thyroid Hormones

18. Thyroid Gland: Highly vascular flat structure.
Located at the upper portion of the trachea.
Composed of twp lobes.

19. Hormones of the Thyroid gland:
Thyroid gland secretes Thyroxin T4 and lesser amounts of
triiodothyronine (T3).
Calcitonin.
Thyroxin and Tiiodothyronin
* Structures: Derived from single amino acid.
Most of the T4 is converted to T3 outside of the thyroid.

20. Structure Activity Relationship
Angle between the two aromatic rings must be 1200.
3’-Monosubstituted molecules are more active than 3’, 5’-disubstituted ones.
Triiodothyronin is 4 times more active than Thyroxin.
3’-Isopropyl derivative is 7 times more active than Thyroxin.
The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), produced by the thyroid gland. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half life than T3. The ratio of T4 to T3 released in the blood is roughly 20 to 1. Thyroxine is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine

21. Regulation:
When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. This is an example of "negative feedback".

22. When blood concentrations of thyroid hormones increase
Stimulation: TRH
Inhibition: -ve Feed-back mechanism.
When blood concentrations of thyroid hormones increase
above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH.

23. Actions of the Thyroid Hormones:
Enhance growth and protein synthesis.
Essential for the development of the nervous system.
Increase oxygen consumption and basal metabolic rate.
Increase body temperature.
Cardiovascular effect:
Increase heart rate.
Increase force of contraction.
Increase cardiac output.
These thyroid hormones influence such bodily functions as:
- A person’s body temperature.
- Mood and excitability
- Pulse rate
- Digestive functions, and other processes necessary for life.

24. Disorders of thyroid function include:
* Hypothyrodisim
- In infants, cretinism
- In adults this cause myxoedema
* Hyperthyrodisim either:
- Diffuse toxic goiter
- Toxic nodular goiter

25. Disorders of thyroid function Hypothyroidism in children (Cretinism)
Irreversible condition due to deficiency of thyroxin
soon after birth.
Retardation in physical and mental development.
Cretinism, is a condition that comes from inadequate thyroid hormones during pregnancy or early infancy.  The brain and the skeleton don’t develop properly and the result can be mental retardation and/or dwarfism.  A child may have a wide and short face, and their top jaw may be very large while their bottom jaw is smaller.  Treatment with thyroid hormone may allow normal and physical development if it is started within the first six weeks of life.

26. Sign and symptoms of Cretinism:
- Mental retardation
- Large head
- Swollen eye lids
- Flattened nose
- Temperature below normal
- Enlarged tongue
- Grows very slowly.
- Poor metabolism
- Thick, dry, cool skin
Cretinism, is a condition that comes from inadequate thyroid hormones during pregnancy or early infancy.  The brain and the skeleton don’t develop properly and the result can be mental retardation and/or dwarfism.  A child may have a wide and short face, and their top jaw may be very large while their bottom jaw is smaller.  Treatment with thyroid hormone may allow normal and physical development if it is started within the first six weeks of life.

27. Disorders of thyroid function Hypothyroidism (Adult)
Myxoedema:
Deficiency of thyroxin in adults due to:
Removal of thyroid gland by surgery.
Destruction of the gland by Radioactive Iodine.
Atrophy of the thyroid gland.

28. Symptoms of Myxedema: Treatment: Thyroxin for life. Muscle weakness.
Slow heart rate and low cardiac output.
Dry cold and thick skin.
Brittle coarse hair.
Puffy expressionless face.
Decreased sweating
Increase body weight and body fat
Treatment:
Thyroxin for life.
Patients also develop a characteristic thickening of the skin which gives myxoedema its name.
eg. :L-Thyroxin sodium
(Synthyroid)

29. Goiter Causes: Lack of iodine in diet. Treatment: Iodine.
Goiter is an enlargement in the thyroid gland (Thyroid Hypertrophy).
Low level of thyroxin.
High level of TSH.
Causes: Lack of iodine in diet.
Treatment: Iodine.
Note: It is important to understand that goiter is not cancer
and that most goiters are, in fact, benign

31. Goiters have different causes depending on their type.
What causes goiter?
Goiters have different causes depending on their type.
Goiters can be classified as:
* Simple or non toxic goiter
* Hereditary
Simple goiters are further classified as:
* Endemic (colloid)
* Sporadic (nontoxic).
Endemic goiters : The use of iodized table salt in the United States has limited the development of this type of goiter; however, iodine deficiency is still common in parts of central Asia and central Africa
Simple goiters are caused by an inadequate supply of thyroid hormone to meet the body’s need. The thyroid gland tries to make up for this deficiency by enlarging

32. Endemic goiters: occur in people within certain geographic areas
who do not get enough iodine in their diet
(iodine is necessary to make thyroid hormone).
Sporadic goiters: have no known cause. Sometimes certain types
of drugs, such as lithium or aminoglutethimide,
can cause this type of goiter.
Hereditary factors also may cause goiters.
* Age over 40
* Family history of goiter

33. Main symptoms of Goiter
A swelling in the front of the neck.
Difficulty breathing, coughing, wheezing
Difficulty swallowing (due to compression of the esophagus).
Hoarseness.
Dizziness when the arms are raised above the head.

34. Other diseases and conditions can also cause a goiter.
These include:
1-Graves’ disease:
Causes: an autoimmune disease (a disease in which your body’s immune system mistakenly attacks your healthy body). In this case, the thyroid gland is attacked, which causes it to over stimulate and results in swelling of this gland.

36. Symptoms: Enlargement in the thyroid gland (Thyroid Hypertrophy).
Increased pulse rate
Increased sweating
High body temperature and flushes.
Hair loss
Inflammation of the eyes
Swelling of the tissues around the eyes
Decrease in body weight and body fat
Nervous excitability
Muscle weakness
Protrusion of the eye ball

37. 2- Hashimoto’s disease:
This is another autoimmune disease. In this case, the disease
causes inflammation of the thyroid gland, which in turn,
results in underproduction of thyroid hormones. Attempts by
other hormones to stimulate the thyroid gland cause it to
enlarge.
3- Thyroiditis:
Inflammation of the thyroid gland itself can result in an
enlargement of the thyroid gland. This can follow a viral
illness

38. Disease Due to Hyperthyroidism
Toxic nodular goiter
- Due to a benign neoplasm or adenoma and may
develop in patients with long-standing simple goiter.
Thyroid cancer. Cancer of the thyroid gland often enlarges the thyroid. Thyroid cancer can be found in thyroid nodules though less than 5 percent of nodules are cancerous. A goiter without nodules is not a concern for cancer.

39. Treatments
A goiter only needs to be treated if it is causing symptoms.
Treatments for an enlarged thyroid include:
Radioactive iodine to shrink the gland, particularly if the
thyroid is producing too much thyroid hormone
Surgery (thyroidectomy) to remove all or part of the gland.
Small doses of Lugol's iodine or potassium iodine solution
if the goiter is due to iodine deficiency
Treatment with thyroid hormone supplements if the goiter
is due to underactive thyroid

40. Calcitonin Site of Secretion: Thyroid gland.
Structures: Peptide Hormones composed of 32 amino acid in
single chain.
Regulations:
By calcium ion concentration:
When calcium ion concentration in plasma increase calcitonin concentration increase and Vic versa.
calcitonin. which may act to lower blood calcium levels.

41. Calcitonin Physiological Functions: Uses: Hypocalcimic effect.
Direct inhibition of bone resorption.
Uses:
Hypercalcimia involving removal of calcium from bones as in Paget’s disease.

43. Parathyroid Hormone (PTH)
Site of Secretion:
Parathyroid gland.
Structure:
Peptide hormones composed of 84 amino acid in single chain.
Parathyroid gland is located in the neck adjacent to the middle & lower portions of the thyroid gland.
Most people have 4 parathyroid glands but more are not uncommon.
Surgical removal of parathyroid gland (hyperparathyroidism) 1/2 glands are removed , the remaining half is sufficient to provide normal parathyroid function.
The parathyroid hormone regulates calcium and phosphate
levels and helps to maintain these levels.

44. Physiological Functions:
Regulation:
By calcium ion concentration:
When calcium ion concentration in plasma decrease PTH concentration increase and Vic versa.
Physiological Functions:
Hypercalcimic effect.
Stimulate mobilization of calcium from bones.
Increase calcium absorption from the intestine.
Decrease calcium excretion and enhance reabsorption.
Stimulate calcium retention by renal tubules.

45. Disorders Hypoparathyroidism:
Due to accidental injury to parathyroid glands during thyroid or neck injury. Patient are unable to maintain their serum calcium without calcium supplementation & develop hypocalcemia

46. Classification Hyperparathyroidism:
It is over activity of the parathyroid glands resulting
in excess production of PTH
Classification
Primary hyperparathyroidism: over secretion of PTH which leads
to hypercalcemia due to adenoma, or, rarely,
carcinoma of the parathyroid glands.
Secondary hyperparathyroidism: occur in response to low calcium
levels, as encountered in various situations such as
vitamin D deficiency or chronic kidney disease.

47. In all cases, the raised PTH levels are harmful to bone, and
Tertiary hyperparathyroidism: result from hyperplasia of the
parathyroid glands and a loss of response to serum
calcium levels.
In all cases, the raised PTH levels are harmful to bone, and
treatment is often needed.
Recent evidence suggests that:
Vitamin D deficiency/insufficiency plays a role in the development of hyperparathyroidism.
Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany

48. Calcimimetic Drugs
These drugs are used to control PTH release from parathyroid glands in patients with primary and secondary hyperthyroidism, without increasing calcium and phosphate levels.
The most common side effects of calcimimetics are mild or moderate nausea and vomiting.
E.g. Cinacalcet HCl “Sensipar”.
It is recognised by the body as if it is calcium, in other words, it mimics the effect of calcium in your tissues. This tricks your body into thinking there is more calcium in the blood which reduces PTH release from parathyroid glands, leading to lower calcium and phosphorus levels in your blood.

49. Growth hormone (GH) Structure:
It is a single polypeptide chain composed of 191
amino acid residues. It has two disulfide bonds.

50. Growth hormone (GH) Secretion: Somatotrophs of the Anterior Pituitary.
Level:
- High in children.
- Maximal during adolescence.
- Lowest during adulthood.
Regulation:
- Stimulation:
ٍ Growth hormone releasing hormone (GHRH)
- Inhibition:
Growth hormone inhibitory hormone (GHIH)
(=somatostatin)

51. Function:
1- It acts on a variety of tissues to stimulate protein anabolism,
lipolysis & hyperglycemia.
2- Promotes growth of tissues.
3- Regulate protein, lipid, CHO & mineral metabolism.

52. Disease Conditions Related to GH
Deficiency:
* Dwarfism ( hyposecretion of GH in children).
Excessive Secretion:
* Giantism (hypersecretion of GH in children):
Due to tumor in somatotrpes in young children or adolescents.
* Acromegaly (hypersecretion of GH in adult):
Rare disease (3/Million).
Causes: Benign tumor of Pituitary gland (90%).
2- Tumors of pancreas, lung or adrenal gland.
Symptoms: Enlargements of extremities.
Non-pituitary Tumors
In a few patients, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH, the hormone that stimulates the pituitary to make GH. In these patients, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.

53. Dwarfism (hyposecretion of GH in children)
Sign & symptoms:
- Children show no abnormalities of intellectual development.
- They appear much younger than their age, not only because
they are short but because their facial feature & body
proportions are immature
Treatment:
- Exogenous GH

54. Gigantism (hypersecretion of GH in children) Sign & symptoms:
- Tall stature (up to 2 ½ meter).
- Mild-to-moderate obesity (common).
- Massive generalized organomegaly.
- Soft-tissue hypertrophy.
Exaggerated growth of the hands and feet
with thick fingers and toes.
- Coarse facial features.
Die at early age, usually due to heart failure.

55. Acromegally (hypersecretion of GH in adult)
Sign & Symptoms:
- Thickening of the palms of the hands and soles of the feet.
- Enlargement of hands (ring size), feet (shoe size) and head
(hat size).
- Enlargement of forehead and jaw, spreading teeth, and
enlarging tongue.
- Arthritis.
- Oily skin and excessive sweating.
- Fatigue, depression.
- Impotence, loss of libido.

56. Treatment of Acromegaly
Transsphenoidal surgery to remove tumor.
Radiation therapy usually follow the surgery.
Drug Therapy:
1- Dopaminergic Agonists:
Bromocriptine (Parlodel®).
2- Synthetic Somatostatin analogs:
Octerotide (Sandostatin®).

57. Prolactin (Prl)
Structure: It is a single polypeptide chain composed of 199
amino acid residues. It has three disulfide bonds.
Secretion:
Prolactin is secreted by the anterior pituitary.
Level:
Starts early in the fetal stages.
Decline shortly after birth and remain low in males.
In female increase with pregnancy reach maximum
level at term and remains high during lactation.

58. The main stimulus for prolactin release is suckling.
Regulation:
Inhibited Prolactin release-inhibiting factor [PRIF] secreted by the hypothalamus is generally held to be dopamine itself.
The main stimulus for prolactin release is suckling.
No hypothalamic stimulation.
Stimulated by TRH but this is of pathological importance.
Physiological Effects:
Breast developments and initiation of lactation.
Note: maintenance of lactation depend on suckling which stimulates a reflex secretion of prolactin by neural pathway, prolactin along with other hormones is responsible for the proliferation of mammary tissue during pregnancy . It inhibits gonadotrophin release and/or the response of the ovaries to these trophic hormones. This is one of the reasons why ovulation does not usually occur during breast feeding and is believed to constitute a natural contaceptive mechanism.

59. Disorders: Causes: Sympotoms: Treatment:
Hyperprolactinemia: hypersecretion of prolactin by lactotroph cells.
Causes:
Tumors in the lactotrophes.
Hypothyroidism associated with high level of TRH.
Hypothalamus or Anterior Pituitary disorders.
Sympotoms:
In females: Galactorrhea, Amenorrhea, Infertility.
In males: Galactorrhea, Impotence, Infertility.
primary hypothyroidism (a high TRH state) can cause hyperprolactinemia
Treatment:
Dopamine agonists: Bromocriptine (Parlodel®)

60. Gonadotropic Hormones
They includes:
1- Luteinizing Hormone (LH).
2- Follicle-Stimulating Hormone (FSH).
3- Chrionic Gonadotropin (CG).
Structures:
- They are glycoproteins.
They were given this name due to their effect on Gonads.

61. Secretion:
LH and FSH are secreted from the Gonadotropes of the Anterior Pituitary.
CG secreted by the placenta. (7 days after ovulation) & remains in the urine & blood of pregnant women up to the end of pregnancy
Regulation:
Stimulation: Gonadotropin-Releasing Hormone from the hypothalamus (GnRH).
Inhibition: Feed back mechanism by sex hormones.

62. Physiological effects: In Males:
LH: Stimulate production of androgens by Leydig cells.
FSH: Enhance normal sperm production by Sertoli cells.
In Females:
LH: Induce Ovulation and stimulate Progesterone production.
FSH: Enhance production of Estrogen and development of follicles.

63. Uses: Diagnostic uses: Diagnosis of Pregnancy: CG in Urine or Blood.
Prediction of Ovulation: LH 36 hr before Ovulation.
Reproductive system disorder in males and females.
Therapeutic uses:
Male infertility.
Female infertility.
Cryptorchidism.
Antagonists:
Used as contraceptives.

64. Function of CG & uses: 1- Diagnosis of pregnancy 2- Diagnosis of ectopic pregnancy 3- Prediction of spontaneous abortion