Follicle-Stimulating Hormone (FSH)

1. Overview

Follicle-Stimulating Hormone (FSH) is a glycoprotein hormone essential for reproductive function in both males and females. It plays a pivotal role in regulating gametogenesis—stimulating ovarian follicle development in females and promoting spermatogenesis in males. FSH works synergistically with luteinizing hormone (LH) and is a key component of the hypothalamic-pituitary-gonadal (HPG) axis. Its secretion is pulsatile and regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus.

2. Location

FSH is synthesized and secreted by the gonadotroph cells in the anterior pituitary gland (adenohypophysis). Its release is triggered by GnRH, which is produced by the hypothalamus and delivered to the anterior pituitary via the hypophyseal portal system. FSH acts primarily on the gonads—ovaries in females and testes in males.

3. Structure

FSH is a glycoprotein hormone composed of two non-covalently linked subunits: an α-subunit and a β-subunit. The α-subunit is common to other pituitary glycoproteins like LH, TSH, and hCG, while the β-subunit is unique to FSH and determines its specific biological activity. The human FSH molecule has a molecular weight of approximately 30 kDa and is glycosylated, which is critical for its stability and function.

4. Function

FSH has distinct roles in male and female reproductive systems:

• In females:

  • Stimulates growth and maturation of ovarian follicles in the follicular phase of the menstrual cycle.

  • Induces the expression of aromatase in granulosa cells, promoting estrogen synthesis.

  • Supports oocyte development and preparation for ovulation.

• In males:

  • Stimulates Sertoli cells in the seminiferous tubules to promote spermatogenesis.

  • Enhances the production of androgen-binding protein (ABP), maintaining high intratesticular testosterone levels.

5. Physiological role(s)

FSH is essential for reproductive development, fertility, and gonadal function:

• Puberty: Rising levels of FSH (along with LH) initiate sexual maturation and gonadal growth in both sexes.

• Menstrual cycle regulation: FSH drives follicular recruitment and selection in the early follicular phase, while also modulating estrogen production.

• Ovarian folliculogenesis: Promotes survival and growth of antral follicles, and works with LH to regulate ovulation.

• Spermatogenesis: Required for initiation and maintenance of sperm production in the seminiferous tubules.

• Feedback control: Estrogen and inhibin B from the ovaries/testes provide negative feedback to regulate FSH levels.

6. Clinical Significance

Abnormal FSH levels can indicate or contribute to various reproductive disorders:

• Elevated FSH:

  • Primary ovarian insufficiency or menopause: Characterized by low estrogen and loss of ovarian follicles, leading to elevated FSH due to lack of negative feedback.

  • Klinefelter syndrome (in males): Testicular failure results in elevated FSH and LH with low testosterone.

• Low FSH:

  • Hypogonadotropic hypogonadism: Caused by hypothalamic or pituitary dysfunction, leading to insufficient GnRH or FSH secretion. May be congenital (e.g., Kallmann syndrome) or acquired (e.g., tumors, trauma).

  • Hyperprolactinemia: Elevated prolactin levels suppress GnRH and thus lower FSH and LH levels.

• Assisted reproductive technology (ART):

  • Recombinant or urinary-derived FSH preparations are used for controlled ovarian hyperstimulation in IVF cycles.

• Diagnostic utility:

  • FSH levels are used to evaluate causes of infertility, assess menopausal status, and diagnose pubertal disorders.