FOLLICLE STIMULATING

HORMONE

AGUSTINUS
 INTRODUCTION

• Follicle-stimulating hormone (FSH)
• A gonadotropin hormone
• Glycoprotein polypeptide hormone
• Synthesized and secreted by the gonadotropic cells of anterior pituitary gland
• 35.5 kDa
• Consisting of two polypeptide units, alpha and beta.
• Similar to those of Luteinezing hormone (LH), thyroid-stimulating hormone (TSH), and human
chorionic gonadotropin (hCG).
• Alpha subunit = 96 amino acids
• Beta subunit = 111 amino acids
 GENE

• Alpha subunit : chromosome 6q14.3

• Beta subunit : chromosome 11p13
• Regulation:
• Stimulated by GnRH & Activin
• Inhibited by inhibin
 FSHR

• G protein-coupled receptor (GPCR)

• Glycoprotein hormone receptor sub-family
• Large extracellular N-terminal ectodomains (ECDs) that bind the heterodimeric
glycoprotein hormones
• FSHR predominantly couples to and activates the Gαs class of intracellular G
proteins, resulting in adenylyl cyclase stimulation, and a subsequent increase in
the second messenger cyclic adenosine monophosphate (cAMP).
• cAMP then binds to and modulates the activity of a number of cyclic nucleotide-
binding proteins, including cAMP-dependent protein kinases, and ion channels.
 FSH LEVEL

• A total of 12,033 data, accounting for 7,491 men (mean age 47.46 ± 13.51
years, range 18–91 years) were studied:
• Testosterone serum levels (mean 5.34 ± 2.06 ng/dL, range 1.70–15.80 ng/dL)
showed a seasonal distribution with higher levels in summer and a direct
correlation to environmental temperatures and daylight duration.
• LH levels (mean 4.64 ± 2.54 IU/L, range 1.00–15.00 IU/L) presented 2 peaks
of secretion in autumn and spring
• FSH levels (mean 5.51 ± 3.24 IU/L) did not show any seasonal distribution. 
 FSH LEVEL

• Before puberty : 0 to 5.0 IU/L

• During puberty : 0.3 to 10.0 IU/L
• Adult : 1.5 to 12.4 IU/L
• FSH level >4.5 IU/L was associated with abnormal semen analysis in
terms of morphology and sperm concentration in the present patient
population (Van Wijngaarden et al., 2011).
• FSH value above 10.36 mIU/mL has sensitivity 82.1% and specificity
79.5% for predicting non-obstructive azoospermia
 ROLE FSH

• Stimulates Sertoli cell proliferation prepubertally

• Determines SC finite number
• Determines the size of the testes
• Antiapoptotic survival factor for spermatogonia, spermatocytes and spermatids
• Supports meiosis and spermiogenesis by regulating the adhesion complexes
between germ and Sertoli cells
• Androgen action is necessary for the completion of meiosis, spermiogenesis
 ROLE FSH

• Gonadotrophin-suppressed men were treated with hCG, i.e. LH-stimulated T

production was achieved in the absence of FSH (Bremner et al., 1981)
• Besides its support of proliferation and development of spermatogonia, FSH
synergizes with T to support spermiation,
• FSH and T cooperation is also indicated by findings that lower doses of either
hormone is effective when the other one is present.
 ROLE FSH

• Paradisi et al (2014) and Ding et al (2015) have observed in placebo-controlled

studies that a high dose of recombinant FSH (300 IU every other day for ≥4-5
months), instead of the standard dose of 75 IU/every other day, significantly
increased sperm counts and pregnancy rates.
• The established clinical indication for FSH use in male infertility is the
treatment of patients with hypogonadotropic hypogonadism
 HISTORY OF FSH TREATMENT

• MacLeod et al:
• Successful therapy with urinary menopausal gonadotropins of a 37-year-old patient who
underwent complete hypophysectomy in 1963
• The patient had provided a semen sample 1 day before the hypophysectomy that showed 576
million sperm per ejaculate and quite good sperm motility and morphology.
• After surgery, the ejaculate quality decreased significantly and, following several weeks after
hypophysectomy, the patient was unable to provide semen samples any more.
• Approximately 14 weeks after hypophysectomy: bilateral testicular biopsy was performed which
showed involution of spermatogenesis to the level of spermatogonia and only few areas with
primary spermatocytes.
• hMG was initiated in the patient one day after the first testicular biopsy, at a dose of
approximately 206 I.U. per day.
 HISTORY OF FSH TREATMENT

• After 64 days of menopausal gonadotropin treatment, another testicular biopsy only of the right testis
revealed stimulated spermatogenesis, showing all stages of spermatogenesis including late elongated
testicular spermatids.
• However, the restoration of spermatogenesis appeared only qualitatively normal, not quantitatively.
• Patient was still unable to produce an ejaculate
• hCG therapy with 4000 I.U. on alternate days was added to stimulate testosterone production by the
Leydig cells.
• hMG dose of 206 I.U. was given no longer daily, but only every second day (alternating with hCG
injections).
• With the combined therapy of hMG and hCG the patient regained the ability to produce an ejaculate
that showed a total sperm count of several million with progressive sperm motility and normal sperm
morphology, that were still decreased compared to the levels analyzed before hypophysectomy
FSH TREATMENT IN MALE
INFERTILITY
TERIMA KASIH