Gonadotropic Hormones

Follicle-stimulating hormone (FSH) and the Luteinizing hormone(LH) are together called gonadotropic hormones or gonadotropins because of their action on gonads.

1.0Gonadotropin-releasing hormone (GnRH)

• GnRH is secreted from the hypothalamus.
• FSH and LH secretion are regulated by the hypothalamic releasing hormone, gonadotropin-releasing hormone (GnRH; also called LHRH). 
• The principal hypothalamic areas involved in ovarian control are the preoptic and supraoptic nuclei.
• Parvocellular neurons in these areas synthesize and secrete GnRH.
• GnRH is a peptide hormone that is produced in the soma as a prohormone and then modified into its active form and secreted into the hypophyseal portal system.The release of GnRH is pulsatile, meaning that there is not a constant release from the hypothalamus. 
• Pulsatile secretion has the advantage of using less energy and does not desensitize target tissue receptors.  
• GnRH is released in a pulsatile manner , and both the pulsatile secretion and the frequency of the pulses have important effects on the gonadotrope. 
• Continuous infusion of GnRH down-regulates the GnRH receptor, thereby resulting in a decrease in FSH and LH secretion. 
• In contrast, pulsatile secretion does not desensitize the gonadotrope to GnRH, and FSH and LH secretion is normal. 
• At a frequency of one pulse per hour, GnRH preferentially increases LH secretion . At a slower frequency of one pulse per 3 hours, GnRH preferentially increases FSH secretion. 
• Gonadotropins increase sex steroid synthesis. 
• The hypophyseal portal circulation delivers GnRH to anterior pituitary gonadotropes, which subsequently secrete LH and FSH.In the absence of GnRH secretion from the hypothalamus, the gonadotropes in the pituitary gland secrete almost no LH or FSH.

2.0The Gonadotrope 

• The gonadotrope secretes FSH and LH (also called gonadotropins) and regulates the function of gonads in both sexes.
• As such, the gonadotrope plays an integral role in the hypothalamic-pituitary-testis axis and the hypothalamic-pituitary-ovarian axis . 
• FSH and LH are segregated into different secretory granules and are not cosecreted in equimolar amounts (in contrast to ADH and neurophysin, for example). 
• This allows independent secretion of FSH/LH by gonadotropes.
• In general, gonadotropins promote testosterone secretion in men and estrogen and progesterone secretion in women. 
• FSH also increases the secretion of a transforming growth factor-β (TGF-β)-related protein hormone called inhibin in both sexes.

3.0Gonadotropic Hormones

LH and FSH, are secreted by the same cells, called gonadotropes, in the anterior pituitary gland. 

LH and FSH are glycoproteins. 

They exert their effects on their target tissues mainly by activating the cyclic adenosine monophosphate second messenger system, which in turn activates specific enzyme systems in the respective target cells.

4.0Functions of FSH and LH

1. Follicle-stimulating Hormone (FSH) 

• Follicle-stimulating hormone is a glycoprotein made up of one α-subunit and a β-subunit. 
• The α-subunit has 92 amino acids and β-subunit has 118 amino acids. 
• The half-life of FSH is about 3 to 4 hours. 

Actions of FSH 

• In males, FSH acts along with testosterone and accelerates the process of spermiogenesis . 
• In females FSH:
• Causes the development of graafian follicles from primordial follicles. 
• Stimulates the theca cells of graafian follicle and causes secretion of estrogen.
• Promotes the aromatase activity in granulosa cells, resulting in conversion of androgens into estrogen . 

2. Luteinizing Hormone (LH) 

• LH is a glycoprotein made up of one α-subunit and one β-subunit. 
• The α-subunit has 92 amino acids and β-subunit has 141 amino acids. 
• The half-life of LH is about 60 minutes. 

Actions of LH 

• In males, LH is known as interstitial cell-stimulating hormone (ICSH) because it stimulates the interstitial cells of Leydig in testes. 
• This hormone is essential for the secretion of testosterone from Leydig cells . 
• In females, LH:

1. Causes maturation of vesicular follicle into graafian follicle along with follicle-stimulating hormone. 

2. Induces synthesis of androgens from theca cells of growing follicles. 

3. Is responsible for ovulation. 

4. Is necessary for the formation of corpus luteum. 

5. Activates the secretory functions of corpus luteum.

Summary of hypothalamic pituitary-testis interactions in the male.

Feedback control of FSH and tonic LH secretion during the follicular phase. 

Summary of hypothalamic pituitary ovarian interactions during the luteal phase of the cycle.

5.0Clinical Uses of Gonadotropins

• The use of gonadotropins in clinical use lies on the principle that gonadotropic hormones act on the ovaries to induce ovulation. 
• The gonadotropins, used widely today, are derived from urine obtained from postmenopausal women. 
• Human gonadotropin can also be obtained from extract of cadaveric pituitary glands. 
• Human pituitary gonadotropin (hPG) is predominantly FSH. It is not easily available. 
• The most commonly used commercial preparation is human menopausal gonadotropins (hMG). 
• One ampoule of hMG (pergonal) contains LH activity of 75 IU and FSH activity of 75 IU. 
• Purified FSH (Metrodin–75 IU/ampoule) is available with minimum LH. 
• Recently, a highly purified preparation of human FSH (Metrodin HP) has been made available (Serono). This is extracted from hMG using anti-hCG antibodies to cause absorption of LH onto gel columns. 
• Metrodin HP can be administered subcutaneously. Recombinant FSH (Gonal F, Recagon) is now available. It is administered by a subcutaneous route. 
• hCG (human chorionic gonadotropin) is known to have a biological action like LH surge and is available in ampoules with 1000–5000 IU (pregnyl, profasi). It is obtained from the urine of pregnant women. 
• Recombinant gonadotropins (FSH, LH and hCG) are used for ovarian stimulation according to the need of individual women and to optimize oocyte quality and cycle fecundity.

Indications 

• Anovulatory infertility where other factors (tubal, uterine, male) have been excluded. 
• Induction of superovulation in assisted reproduction.
• hCG is administered for luteal phase support especially when GnRH agonist is used. 
• Treatment of male infertility (hypogonadotropic hypogonadism) 
• Treatment of cryptorchidism. 
• Unexplained infertility. 

Contraindications 

• High level of endogenous FSH, indicating ovarian failure . 
• Overt thyroid or adrenal dysfunction. 
• Pituitary tumor. 
• Indeterminate uterine bleeding