Overview of Gonadal Function

Question 1

What is the structure of Gonadotrophins LH and FSH?

Answer 1

• FSH and LH are both glycoproteins consisting of 2 subunits
• Common α–subunit (also common to TSH and hCG)
• β-subunit unique to each hormone

Question 2

How is Gonadotrophin release regulated?

Answer 2

• Synthesis and release of both LH and FSH is under the control of gonadotrophin releasing hormone (GnRH)
• GnRH secreted episodically resulting in pulsatile secretion of LH and FSH with peaks every 90 mins

Question 3

What is the function of the Gonads in females?

Answer 3

• Ovum (egg) production
• Production of sex steroids (androgens and oestrogens)

Under regulation by FSH and LH

Question 4

What is the progression of the egg cell ?

Answer 4

• Primodial follicles
• Primary follicles
• Mature follicle

Meiosis 1 completed the day before ovulation to form secondary oocyte (haploid cell) and polar body

• Secondary Oocyte
• Ovulated egg (contains corona radiata, zona pellucida, secondary oocyte)
• Corpus Luteum

Question 5

How does the egg mature?

Answer 5

• Primordial follicle
• Early Preantral Follicle
• Late preantral follicle
• Antral follicle
• Preovulatory or Graffin follicle

Question 6

What are cells found in the Ovary and their purpose?

Answer 6

• Theca Cells (cells of theca interna)
• Granulosa Cells
• Corpus Luteum

Question 7

What is the function of the Corpus Luteum?

Answer 7

• The mature follicle releases its ovum when it is up to 2cm in diameter. Residual cells of the follicle form the corpus luteum
• Switch to production of progesterone from Estradiol
• Progesterone acts on the breast to stimulate glandular development
• Stimulates secretory & vascular activity of endometrium to prepare for implantation of embryo. Supports early pregnancy.

Question 8

What is the purpose of the Theca cells?

Answer 8

Synthesise androgens, mainly androstenedione and testosterone.

Question 9

What are the functions Granulosa cells?

Answer 9

• Utilise testosterone from theca cells to synthesise oestradiol (E2)
• Synthesise inhibins - two chain polypeptide which feeds back on the pituitary to reduce FSH but not LH, and AMH (anti mullerianhormone)

Question 10

What is used to produced sex steroids?

Answer 10

Cholesterol

Question 11

How does the FSH affect the gonads?

Answer 11

• Stimulates follicular cells of ovary to produce steroids by activating aromatase & P450 enzymes. Produces follicular phase E2 and Luteal phase progesterone
• Surge at mid cycle with LH triggers ovulation
• Negative feedback on gonadotrophin releasing hormone (GnRH) production by hypothalamus

Question 12

How does the LH affect the gonads?

Answer 12

• Stimulates theca cells to produce steroids, androstenedione & testosterone
• Surge at mid cycle triggers ovulation
• LH turns follicle into corpus luteum by triggering ovulation

Question 13

What is Inhibin?

Answer 13

• Glycoprotein with α-subunit and one of 2 β-subunits – inhibin A (βA) inhibin B (βB)
• Secreted by granulosa cells under action of FSH
• Act to inhibit FSH production and GnRH release from hypothalamus
• Inhibin A peak mid luteal phase, B early-mid follicular and mid cycle

Question 14

What is Activin?

Answer 14

• Dimers of inhibin β-subunit activin A, AB, B dimers of βA, βAβB, βB
• Act to oppose action of inhibins
• Stimulates FSH secretion
• Enhances androgen synthesis under LH contr

Question 15

What is Anti mullerian hormone and where is in produced?

Answer 15

• Structurally related to inhibin and activin. Dimeric glycoprotein 140kDa
• Produced by the granulosa cells of preantral (primary and secondary) and small antral follicles in the ovary (also Sertoli cells in males)
• AMH production starts following transition from the primordial to primary follicular stage and continues until the follicles reach the antral stage

Question 16

How does AMH change through life?

Answer 16

• Remains low in females at birth rising with age to puberty. High levels of AMH then slowly decline until menopause when fall rapidly.
• No intercycle variability
• AMH concentration is proportional to egg maturation potential or “ovarian reserve”
• AMH inhibits excessive follicular recruitment by FSH

Question 17

What is Menopause?

Answer 17

• Ovaries stop producing ova and sex steroids 30-40 years
• Cause is unknown. The supply of ova has not yet been exhausted, however the ovaries become resistant to stimulation by gonadotrophins

Question 18

How does the biochemistry change in menopause?

Answer 18

• Basal FSH concentrations rise first followed by LH
• Ovulation and production of Estradiol eventually fails (may take 2 years)

Clinically menopause defined by cessation of menstruation for 1 year

Question 19

What are test results of stages in gondal function?

Answer 19

Follicular Phase

• LH: 2.4-12.6
• FSH: 3.5-12.5
• Oestradiol: 45-854

Mid cycle peak

• LH: 14-95.6
• FSH: 4.7-21.5
• Oestradiol: 151-1461

Luteal phase

• LH: 1-11.4
• FSH: 1.7-7.7
• Oestradiol: 82-1251

Question 20

How does biochemistry results appear in menopause?

Answer 20

Menopause

• LH: >15
• FSH: >30
• Oestradiol: <50

Question 21

How do biochemistry results appear in Hypopituitary states and Pregnancy?

Answer 21

Hypopituitary

• LH: Low
• FSH: Low
• Oestradiol: Low

Pregnancy

• LH: suppressed
• FSH: suppressed
• Oestradiol: high

Question 22

How do biochemistry results appear in males?

Answer 22

Males

• LH: 1.7-8.6
• FSH: 1.5-12.4
• Testosterone: 8.6-29

Hypogonadotrophic hypogonadism

• LH: Low
• FSH: Low
• Testosterone: Low

Primary testicular failure

• LH: High
• FSH: High
• Testosterone: Low

Question 23

What are the main function of testis?

Answer 23

• Production of testosterone (main male sex steroid)
• Site of spermatogenesis

Question 24

How is the testis regulated?

Answer 24

Regulated by

• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)

produced by the anterior pituitary

Question 25

What are the cells of testis?

Answer 25

Seminiferous tubules

• Germ cells develop into sperm through a process of spermatogenesis. Contain DNA for fertilisation of ovum.
• Sertoli cells (epithelium) support germ cell development. Secrete inhibin and AMH

Leydig cells

• Localised between seminiferous tubules
• Secrete testosterone and other androgens

Question 26

How does FSH affect the testis?

Answer 26

• Stimulates Sertoli cells to stimulate spermatogenesis
• Stimulates Sertoli cells to produce inhibin which provides negative feedback on FSH secretion by pituitary

Question 27

How does LH affect the testis?

Answer 27

• Stimulates Leydig cells to produce testosterone
• Testosterone provides negative feedback to pituitary & hypothalamus (GnRH, gonadotrophin releasing hormone secretion)

Question 28

What is the action of Inhibin in males?

Answer 28

• Secreted by Sertoli cells under action of FSH
• Act to inhibit FSH production and GnRH release from hypothalamus

Question 29

What is the action of AMH in males?

Answer 29

• •Very early involvement in male foetus
• AMH secretion inhibits development of female reproductive organs (Mullerian ducts) resulting in testis formation (Wolffian ducts) – needs testosterone
• Very high at birth to puberty, can be >1000pmol/L, falls post puberty