A BRIEF NOTES ON ANTERIOR PITUITARY HORMONES[ PHARMACOLOGY ] WHICH WILL BE USEFUL FOR PHARMACY STUDENTS. IT IS ACCORDING TO THEIR SYLLABUS.

1. ANTERIOR PITUITARY
HORMONES
NITESH KUMAR
B.PHARM (6TH SEM)
JCP, JAIPUR
SESSION-2017-2021

2. ANTERIOR PITUITARY
HORMONES
Pituitary gland = Master gland = Adenohypophysis +
Neurohypophysis.
- Secreted by the anterior lobe of pituitary gland.
-Secretion is regulated by the hypothalamus
through release hormones and release inhibiting
hormones [RIH].
-Anterior pituitary hormones are produced by
separate group of cells such as somatotrophs,
lactotrophs, corticotrophs, gonadotrophs and
thyrotrophs.

3. CLASSIFICATION
• 1. SOMATOTROPIC HORMONES
A. Growth hormones [GH]
B. Prolactin [Prl]
2. GLYCOPROTEIN HORMONES
A. Luteinizing hormone [LH]
B. Follicle hormones [FH]
C. Thyroid stimulating hormones [TRH]
3. PRO-OPIOMELANOCORTIN DERIVED
HORMONES
A. Corticotropin : ACTH [ Adrenocorticotropin]
B. Melanocyte stimulating hormones : a-MSH, b-MSH
C. Lipoproteins : beta-LPH, gamma- LPH.

4. GROWTH HORMONE [GH]
-- Single polypeptide chain of 191 amino acid
residues.
-- Structural similarity with prolactin.
-- Secreted by somatotrophs of the anterior
pituitary.
-- Molecular weight – 22,000.
-- Synthesized and stored by the somatotrophs of
adenohypophysis which form 50% of total cells of
the anterior pituitary.
PLASMA LEVEL
-- High in children, maximal during adolescence.
-- Decreased with ageing.

5. REGULATION
Stimulation - By GNRH [ Somatorelin]
Regulation- By GHRIH [ Somatostatin]
- Factors stimulating release
- Hypoglycemia - Exercise
- Stress - Ghrelin
- Factors inhibiting release
- Free fatty acids - Corticosteroid
- Hyperglycemia
MOA
-- Via JAK/STAT [ Janus Kinase- Signal Transducer and
activator of Transcription ] cytokine receptor super family.
-- Induce Conformational change.
-- Recruitment and activation of JAK kinase.
-- Phosphorylation.
-- Dimerization.
-- Nuclear translocation.

6. PHYSIOLOGICAL EFFECTS
1. DIRECT EFFECTS
a. Stimulation of lipolysis .
b. Stimulation of hepatic glucose output.
c. Production of insulin like growth factors.
d. Catabolic effects in lipid cells and
anabolic effects muscles.
e. Mixed effects on carbohydrates
metabolism.
f. Increase protein synthesis.
2. INDIRECT EFFECTS.
a. Increase cell members.
b. Positive nitrogen balance .
c. Increase protein synthesis.
HYPERSECRETION OF GH – Gigantism in children.
-- Acromegaly in adults.
HYPOSECRETION OF GH - Dwarfism

7. • USES
- Childhood pituitary dwarfism
- Idiopathic short stature.
- Growth
- Increase lean body mass and weight
- Short bowel syndrome
- Athlete dope drug
- Wasting n HIV patient.
ADVERSE EFFECTS
- CHILDREN – Nausea, Vomiting and Scoliosis
- ADULTS - Peripheral edema, Arthrlgia Myalgia, Otitis Media.
AGONIST 1. MECASERMIN
-- Combination of recombinant IGF-1 AND IGF-3.
-- Used in IGF-1 deficiency, growth failure and persons
with antibody associated
GH resistance.
Dose -- 40-80 mcg/kg SC.

8. Antagonist
1. SOMATOSTATIN
-- Contains 14 AA, secreted by hypothalamus and
delta cells of islets of langerhans.
-- T ½ life =2-3 min.
P’COLOGICAL EFFECTS
-- Inhibits prolactin, TSH, Insulin, glucagon.
-- Inhibit GIT secretions [ gastrin, billiary
pancreatic.
-- Vasoconstriction of hepatic splanchic vessels.
A/E ---- Dyspepsia, Achlorhydria, Steatoorhea, Nausea, Diarrhea
and Hypochlorhydria.
Uses ---- i> For controlling acute bleeding from esophageal varices and
peptic ulcer.
ii> As an adjuvant in diabetic nephropathy.
Analogues of somatostatin
i> Lanreotide, vapreotide and seglitide.
2. OETREOTIDE
3. PEGVISOMANT

9. PROLACTIN
• Single polypeptide chain of 199 amino acid.
• Secreted by lactotrophs of the anterior pituitary.
• Secretion starts early in the fetal stage, decline shortly after birth and
remain low in male.
• In female it increases with pregnancy.
• Maximum at parturition.
REGULATION
Inhibition – By dopamine and its agonists.
Secretion – By TRH, VIP, PRP, Sleep, stress suckling,
chronic renal failure, hypoglycemia and
hypothyroidism.
PHYSIOLOGICAL EFFECTS
-- Proliferation and differentiation of mammary tissue.
-- initiation of lactation.
MOA
-- Binds to prolactin receptors and activates the cytoplasmic
JAK-STAT tyrosine protein kinases. This result in endocrine
and metabolic effects of prolactin.

10. PHYSIOLOGICAL EFFECTS.
• Promotes growth and development of breasts during pregnancy.
• Induces and maintain milk secretion after parturition.
• Stimulates the synthesis of lactose and milk proteins.
• Inhibits spermatogenesis and decrease the plasma testosterone
levels in males.
• Enhance the absorption of calcium resulting in bone development.
• Promotes the growth of B-cells of pancreatic islets.
• Increases appetite and inhibit GnRH.
ANTAGONIST
1. BROMOERGOCRIPTINE
-- Ergot derivative.
-- Selective agonist of D2 receptors, weak agonist or
antagonist of D1 receptors and a weak alpha adrenergic
blocker.

11. P’COKINTEICS
-- Orally or parenterally.
-- Absorbed from GIT.
-- Crosses BBB and undergoes extensive 1st pass
metabolism.
-- Plasma t 1/2 life – 3-6 hrs.
-- Eliminated through Bile.
-- 6-7% through Kidneys.
P’COLOGICAL EFFECTS
-- Inhibit the synthesis and release of prolactin.
-- Causes behavioral changes.
-- Increases the plasma GH levels.
-- Acts as an anti-parkinson drug.
-- Decrease BP.
A/E – Nausea, Vomiting, Gastric upset, drowsiness,
Hallucinations, mental confusion.
USE -- for treating hyperprolactinaemia, galactorrhoea syndrome,
prolactinoma, acromegaly, DM and parkinsonism.

12. 2. CABERGOLINE
-- Long acting and more potent analogue of
bromocriptine.
-- Newer D2 agonist employed in individuals resistant to
bromocriptine.
-- Its plasma t ½ = 60 hrs.
A/E -- Nausea, vomiting, abdominal pain, epitasis, half
blindness, palpitations and hot flushes.
USE -- Used for treating hyperlactinaemia and acromegaly.
AGONISTS
1. BROMOCRIPTINE
-- 1.25 mg after evening meal.
Use -- parkinsonism, acromegaly and hepatic coma.
2. QUINAGOLIDE
3. CABERGOLINE.

13. GONADOTROPINS
• Glycoprotein's [23-28 %] secreted by gonadotropins in
anterior pituitary lobe.
• Include
-- follicle stimulating hormones
-- luteinizing hormones
-- human chorionic gonadotropins
i> FSH – alpha chain [92 AA] and beta chain [ 111 AA]
MW= 33KD
ii> LH -- alpha chain [ 92 AA] and beta chain [ 121 AA]
MW = 30 KD
MOA -- Activation of specific FSH and LH G- proteins coupled
receptors by gonadotropins stimulates the conversion of
cholesterol to pregnenolone and production of gametes.
PREGNENOLONE– First step in the synthesis of estrogen,
progesterone and testosterone.

14. • SECRETION
LH and FSH – Gonadotrophs of the anterior pituitary.
HCG – Placenta
• REGULATION
Stimulation – gonadotropin releasing hormones [ GnRH]
Inhibition -- feedback mechanism by sex hormones.
-- CG produced by placenta after fertilization.
• PHYSIOLOGICAL EFFECTS
[MALES] LH- Stimulates production of androgens by leydig
cells.
FSH– Enhance sperm production of sertoli cells.
-- regulate spermatogenesis.
[FEMALES] LH-- Induce ovulation and stimulation
progesterone production.
-- maintenance of corpus luteum.
-- stimulate synthesis of testosterone and
androstenedione.
FSH – Enhance production of estrogen and
development of follicles and ovum.

15. • USES
Diagnostic - diagnosis of pregnancy : HCG in urine or blood.
- prediction of ovulation : LH 36 hr before ovulation.
- ovustick : immunoassay dipstick test.
- reproductive system disorder in males and females.
Therapeutic--- A. ovulatoryinduction
-- in anaovulatory women.
-- hypogonadotropic gonadism, PCOD, obesity.
-- failure of less complicated treatment.
-- treatment protocol based on normal menstrual cycle.
-- from 3rd day to 10th day or urofollitropin.
-- next day HCG 10000 IU.
B. MALE INFERTILITY
1. HCG- 1000-2500 IU per week for 8-12 weeks.
2. HMG – 75-150 units three times per week.
3. ICSI – Intra cytoplasmic sperm injection.
4. -- for controlled ovarian hyperstimulation
5. -- cryptorchism
6. -- to aid invitro fertilization.
S/E -- Ovarian hyper stimulation, multiple pregnancy, precacious puberty,
headache, depression, oedema and risk of gynaecomastia.

16. GONADOTROPIN RELEASING HORMONE
-- Polypeptide composed of 10 AA residues.
SECRETION
-Hypothalamic neurons with onset of puberty.
Pulsatile GnRH secretion – stimulates gonadotropin secretion.
Non-pulsatile GnRH secretion- Inhibits gonadotropin secretion.
i> GONADORELIN
- acetate salt of synthetic human GnRH.
-- administered SC/IM.
-- t ½ life – 4-8 min.
-- used for testing pituitary gonadal axis in male as well as female
hypogonadism.
GnRH ANALOGUES
-- goserelin, (SC/IM/NASAL SPRAY)
-- Histrelin, nafarelin, triptorelin and leuprolide
-t ½ life = 3 hrs.

17. P’CODYANAMICS
- Exhibit complex dose response relationship.
- during fetal life – pulsatile GnRH release.
-- from age 2 yrs. To puberty-GnRH secretion just falls before puberty.
-- increase in amplitude and frequency of GnRH secretion.
follicular phase – higher frequency
luteal phase -- higher amplitude.
USE
1. Due to stimulation
a> female infertility – very rarely used.
b> male infertility - 3-6 months treatment is required.
c> diagnostic of LH responsiveness.
2. By suppression
a> long acting GnRH in a continuous fashion.
-- precocious puberty ( 1.6 mg/d)
-- prostate cancer.
b> long acting analogue ( leuprolide, histrelin )
-- uterine leiomyoma, endometriosis
-- estrogen dependent breast cancer
-- controlled ovarian hyper stimulation.

18. S/E -- 1. FEMALE
-- headache, nausea, flushing, local swelling,
hypersensitivity, dermatitis and blindness.
On continuous treatment – typical symptoms of menopause
-- hot flush, sweating, depression,
pain, vaginal bleeding, dryness and breast atrophy.
C/I IN FEMALES --Pregnancy and breast feeding.
2. MALES
-- Hot flush, sweating, edema, gynecomastia,
decreased libido, asthenia and bone density.
GnRH ANTAGONIST
-- Ganirelix, abarelix, cetrorelix and degarelix
USE -- 1. Controlled ovarian stimulation to prevent LH surge.
2. advance prostate cancer.
S/E -- Nausea, headache, abarelix- allergy, hypotension and
QT prolongation

19. ADRENOCORTICOTROPIC HORMONE
-- 39 AA polypeptides
MW – 4500
-- synthesized as part POMC.
-- responsible for the stimulation of synthesis and release of cortisol by
adrenal cortex.
Release regulated by – Corticotropin releasing hormones. [CRH]
Stimulated by - stress and hypoglycemia.
-- circadian pattern of release.
-- highest level of cortisol are in early morning.
-- depends on sleep awake cycle.
-- Jet-lag can result in alteration of pattern.
-- action is through MCR (GPCR).
-- mostly MC2R.
ACTS -- i> stimulates growth of adrenal cortex.
ii> stimulation of steroid hormone synthesis.
Excess production – cushing’s syndrome.
Deficiency -- pituitary insufficiency.

20. MOA
-- ACTH binds to specific cell surface GPCRs and activates adenylyl
cyclase system resulting in increased levels of [cAMP] in cortisol cells which
in turns promotes the conversion of cholesterols to pregnenolone from which
various adrenocortical steroids are obtained.
PHYSIOLOGICAL EFFECTS
-- It stimulates the production of glucocorticoids, mineralocorticoids
and androgens by adrenal cortex.
-- Causes ketosis, lipolysis in adipose tissue, pigmentation of skin and
insulin resistance.
AGONIST
A. COSYNTROPIN
-- synthetic human ACTH.
-- 39 AA
-- Given by IM or IV.
-- T ½ - 15 min.
USES – i> less predictable, less consistent than coticosteroid
ii> some times use for multiple sclerosis.
iii> testing integrity of HPA axis.
A/E -- Hyperandrogenism, no retention and hypokalemia.

21. THYROID STIMULATING HORMONE [TSH]
-- 210 AA, two chain glycoprotein, MW- 30,000
-- Stimulate thyroid glands – secrete T3 and T4.
-- induce hypertrophy and hyperplasia of thyroid follicles.
-- promote iodide trapping
-- promote organification of and incorporation of iodine.
MOA -- TSH binds to TSH receptors and activates the adenylyl cyclase[cAMP ]
system which results in effects produced by TSH.
REGULATION -- Thyroid releasing hormones of hypothalamus controls the synthesis
and release of TSH.
Inhibition by – T3 and T4
-- Somatostatin and dopamine.
AGONIST 1. THYROTROPIN ALPHA
-- Recombinant human TSH having a t ½ life of 22-24 hrs.
A/E -- Asthenia [ weakness and loss of strength] nausea and
headache.
USE -- no therapeutic use but used for differentiating myxoedema
caused due to thyroid and pituitary dysfunction.

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