MK - Endocrine Pharmacology III

Question 1

How do the hypothalamus and anterior pituitary work together to stimulate sex hormones? (4)

Answer 1

1. Hypothalamus stimulates the production of GnRH
2. GnRH acts on the anterior pituitary to release FSH and LH
3. FSH acts on the Graaafiean follicle (GF) which causes the release of oestrogens
4. LH acts on the corpus luteum (CL) which causes the release of progesterone

Question 2

Where do oestrogens and progesterones act? (2)

Answer 2

1. Oestrogens and progesterone act on reproductive tracts and other tissues
2. Also, cause negative feedback and inhibit the release of GnRH from the hypothalamus and the release of FSH and LH from the pituitary

Question 3

What are 5 key points about sex hormones?

Answer 3

• FSH stimulates growth of ovarian follicles (each follicle contains one oocyte)
• 17b oestradiol is produced by growing follicles. 17b oestradiol negative feedback prevent excessive FSH production
• In humans only one follicle fully matures (Graafian Follicle- GF)
• 17b oestradiol triggers release of Luteinising Hormone
• Ovulation triggered by an LH rise

Question 4

Features of progesterone (5)

Answer 4

• GF forms corpus luteum (CL) after ovulation. CL produces hormone progesterone (and some 17b oestradiol)
• Progesterone stimulates uterus for embryo implantation
• Progesterone prevents formation of new CL by inhibiting FSH release
• Progesterone= hormone of pregnancy
• Progesterone stimulate cervix to produce a mucous that prevents sperm entry

Question 5

What are 3 types of oestrogens?

Answer 5

• 17b-oestradiol (E2)
• Oestrone (E1)
• Oestriol (E3) in pregnancy

Question 6

Major uses of oestrogen drugs (4)

Answer 6

1) Primary hypogonadism: stimulates the development of secondary sexual characteristics and accelerates growth in children.

2) Primary amenorrhoea (no periods): induces an artificial menstrual cycle in adults

3) Contraception: as an oral contraception in women. Given with a progestogen

4) Hormone Replacement Therapy (HRT): Given to women at or after the menopause

• HRT helps physical symptoms of menopause and bone loss (osteoporosis).

Question 7

What are the 2 hormones present in oral contraceptives and 3 types of formulation?

Answer 7

estrogen: ethinyl estradiol
progestin: norethindrone

Three types of formulation: monophasic, biphasic and triphasic

Question 8

How do oral contraceptives work and what are the adverse effects? (4)

Answer 8

Act by providing negative feedback to the pituitary and shut down secretion of LH and FSH

Adverse effects:

• Abnormal menstrual bleeding
• Hypertension
• Increased appetite, weight gain
• Nausea, oedema, breast tenderness

Question 9

What are anti-progestogens?

Answer 9

• Medical termination of pregnancy (abortifacient): mifepristone (RU-486). Emergency ‘Contraception’
• Endometrial shedding and embryo loss from the site of implantation; cervix softening

Question 10

What are features of anti-oestrogens?

Answer 10

1) Oestrogens bind nuclear receptors in target cells

2) Oestrogen receptors are: Estrogen Receptor α (ERα) and Estrogen Receptor β (ERβ)

• There are multiple forms of ERα and ERβ

3) A tissue can have just one type of ER (e.g. brain regions) or both (e.g. prostate)

4) Due to the variety of ER’s, actions of anti-oestrogens can be varied and tissue-specific

Oestrogens bind nuclear receptors in target cells (ERα or ERβ) modification of gene transcription

Question 11

What is an example of a non-steroidal oestrogen antagonist?

Answer 11

Clomiphene – induces ovulation by reducing negative feedback inhibition of oestrogen on the hypothalamus and anterior pituitary gland

Question 12

How is clomiphene used in fertility treatment for anovulation? (3)

Answer 12

1. Clomiphene allows FSH and LH levels to rise = no negative feedback inhibition of oestrogen
2. Raised FSH allows more follicles to grow
3. Raised LH eventually triggers ovulation

Question 13

What are SERMS (Selective oEstrogen Receptor Modulators) and what are 2 examples?

Answer 13

Competitive antagonists or partial agonists of oestrogen- ER binding

• SERM-Tamoxifen is used in oestrogen-dependent breast cancer
• SERM-Raloxifene is used to treat postmenopausal bone loss

Question 14

What are 4 treatments of insulin related to Oral hypoglycaemics?

Answer 14

1) Sulfonylureas e.g. Glibenclamide;
Inhibit KATP channel

• Accumulation of K+ inside resulting in depolarisation of beta cells; insulin secreted

2) Biguanides e.g. Metformin
Inhibit gluconeogenesis

3) Alpha-glucosidase inhibitors e.g. Acarbose
Delay carbohydrate absorption

4) Thiazolidinediones (Glitazones) e.g. Pioglitazone;
Bind to a nuclear receptor (the peroxisome proliferator-activated receptor (PPAR)gamma) to regulate the transcription of genes in fat cells and other tissues