Nematodes

Gonadotropin-releasing hormone (GnRH) 

Introduction

It is also called the central hormone or mother hormone of reproduction.
The reason; GnRH causes the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone). Both these hormones act on the testis in males and ovaries in females. Testis will produce sperms and the ovary will produce the egg, both of these gametes combine and cause pregnancy, while ovaries also produce P4 (progesterone) that maintain pregnancy, and E2 (estradiol) female sex hormone that controls the reproductive behavior of female. Due to these above reasons, GnRH is called the mother hormone.

Source: Hypothalamus
Action: Anterior pituitary
Function: FSH and LH release
It is a small molecule and has decapeptides (contains 10 amino acids). When we inject it in the body it undergoes proteolysis (degrade at bond 5-6, 6-7, and 9-10 of amino acids). Now we make synthetic GnRH by replacing with other amino acids at 6 (glycine) and 10 (glycine) amino acids. At number 6 we replace glycine with some other amino acids while at point 10 we always replace glycine with ethyl amide.

Functions of FSH

In male

• It regulates the functions of Sertoli cells.
• It causes the production of androgen binding protein by Sertoli cells.
• Production of estradiol by Sertoli cells (SC).

In female

• It is responsible for early follicular growth.
• It is responsible for the production of E2 by granulosa cells.

Functions of LH

In male

• It is responsible for the production of testosterone by Leydig cells.

Lydig cells are also known as interstitial cells. This hormone is also known as interstitial cell-stimulating hormone (ICSH).

In female

• It causes luteinization (CL formation).
• It acts on both, granulosa cells and theca interna cells.
• Granulosa cells form large luteal cells while theca interna forms small luteal cells.
• It causes ovulation.
• It causes late follicular growth or the maturation of graffian follicles occurs by LH.

Release of GnRH, FSH, and LH

FSH and LH are released by gonadotrophs. The anterior pituitary has 10-15% gonadotrophs. Gonadotrophs are basophilic. GnRH is released by the arcuate nucleus, ventromedial nucleus, and pre-optic nucleus.

Composition

FSH and LH are collectively called as Pituitary gonadotropins. There are two gonadotropins and 2 placental gonadotropins (eCG and hCG).
FSH and LH are glycoproteins and composed of 4 chains; 2a (alpha) and 2B (beta) subunits.
a-subunits are same but B-subunits are different.
FSH: 
            a_________
            B_________
            B_________
             a_________
LH:
           a_________
           B-------------
           B-------------
           a_________
eCG:
          a__________
          B...................
          B...................
          a__________
hCG:
            a_________
            B_________
            B_________
            a__________
All have same a (alpha) subunits.
eCG and HCG are produced by chorion of placenta. They are only produced in pregnant females. The cells of chorion are called Trophoblastic cells.
eCG is also known as PMSG (pregnant mare serum gonadotropin)

Functions of hCG (human chorionic gonadotropin)

It is detected at day 10 of gestation.

• It acts as luteotropic i.e., it supports C.L or helps C.L. in progesterone production. LH causes progesterone production by CL. hCG is LH like.
• Helps in the development of fetal gonads (testis) and renal glands in the male.
• In all non-human species like camel or cow, it acts as LH like.

eCG

 It is released only in pregnant female equines.
Source: Chorionic placenta
It is detected as early as 30-40 days of pregnancy in serum. It is a large molecule and is not filtered by the kidney, so that it is not present in urine. It is always detected in serum, so-called pregnant mare serum gonadotropin (PMSG).

Functions of eCG (equine chorionic gonadotropin)

• Formation of accessory CL in mare (Cl will produce P4).
•  In mare, it acts like LH.
• In all other species except mare, it acts as FSH.

Composition

1. LH contains 22%  carbohydrates and the remaining is protein. Its half-life is 30 minutes to 1 hour.
2. FSH contains 28% carbohydrates and the remaining is protein. Its half-life is 2-3 hours.
3. eCG contains 45% carbohydrates and the remaining is protein. Its half-life is up to 2 days (> 2 days).
4. hCG contains 33% carbohydrates and the remaining is protein. Its half-life is 24 hours.

Clinical uses of GnRH or its functions (FSH, LH, eCG, hCG)

It is used for

1. Treatment of plain ovaries; do not have follicular growth. ( we can give GnRH, FSH, or eCG).
2. Treatment of delayed ovulation at the time of artificial insemination (A.I). Follicles will be aged, not fertilize, and degrade. (we can give GnRH, LH, or hCG).
3. Can be used to improve pregnancy rate. GnRH increases P4 production from CL. Use GnRH, FSH, or ECG at day 12th of pregnancy.
4. To induce ovulation. Give GnRH, LH, or hCG at the time of A.I or after mating.
5. For the treatment of follicular cyst. (Cyst: Follicle which does not ovulate). Use GnRH, LH, or hCG.
6. Used for breeding management in mare. Give GnRH, LH, or hCG
7. Use GnRH, LH, or hCG to curtail (shorten) long pro-estrus in bitch.
8. Use in dogs, cats, and zoo animals (lions, tigers, etc).
9. For superovulation, use FSH or ECG instead of GnRH.

To inhibit or prevent fertility or cyclicity

1. GnRH antagonist

2. GnRH agonist

 They act like GnRH but they are stronger and more potent than GnRH. Give GnRH continuously or implant GnRH in the body for a longer period of time. It releases slowly from the implantation site. Initially, it causes increased cyclicity but when it is present all the time in blood, pituitary glands will desensitize ultimately to GnRH action and inhibits fertility.

3. GnRH toxin conjugates

 Once toxin enters inside the pituitary cells, it will cause the cells to die, and ultimately there will be no FSH and LH production.

Types of GnRH agonist

1. Deslorelin: it is 144 times more potent than GnRH of the hypothalamus. It is only the one agonist used in veterinary practice. Its brand name is Suprelorin R.

These listed below are used for human

1. Buserelin: it is 20 times more potent than GnRH of the hypothalamus
2. Fertilin
3. Gonadorelin
4. Lecirellin
5. Histrelin: Most potent of all agonists.  It is214 times more potent than GnRH of the hypothalamus