Hypothalamic and Gonadal
Components of Hypogonadism in Boys with Prader-Labhart-Willi Syndrome
Urs Eiholzer, Dagmar LíAllemand, Valentin Rousson, Michael Schlumpf, Theo
Gasser, Jurg Girard, Annette, Gruters, and Manuela Simoni
Journal of Clinical Endocrinology & Metabolism 2006;
Summary by Jamie H. Bassel, D.C., P.C.
A study performed at the Institute of Growth Puberty and
Adolescence in Zurich, Switzerland focused on uncovering the mystery behind the
type of hypogonadism typically seen in PWS males. The objective was to
determine the specific cause of Gonadal deficiency. The cause
of hypogonadism may be "primary" or "central." In primary hypogonadism, the
testes themselves do not function properly. In central hypogonadism, the centers
in the brain that control the gonads (hypothalamus and pituitary) do not
function properly. The design of the study placed 2 sets of PWS boys ( 8
infants and 6 around the age of puberty) . Each group was given injections of
hCG (human chorionic gonadotropin) of varying concentrations (2x500-1500 U on a
weekly basis) and was followed from the onset of puberty (13.5 years through the
time of publication).
The following levels were monitored closely serum Follicle
Stimulating Hormone (FSH), Luteinizing Hormone (LH).
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are
called gonadotropins because stimulate the gonads - in males, the testes, and in
females, the ovaries. LH stimulates secretion of sex steroids from the gonads.
In the testes, LH binds to receptors on Leydig cells, stimulating synthesis and
secretion of testosterone. FSH is important for
sperm production. It supports the function of Sertoli cells, which in
turn support many aspects of sperm cell maturation.
Inhibin B and Testosterone were also monitored in this
study. The inhibin concentration is higher in men with apparently normal
fertility than in those with infertility and abnormal sperm production. Serum
Inhibin B is the direct serum marker of sperm production in men with testicular
The researchers also closely followed the
patientís overall skeletal development. The results demonstrated that infants
with PWS had normal LH and Testosterone Levels when compared to infants without
PWS. It was noted that 67% of the PWS infants in this study had undescended
testes. Inhibin B levels were considered significantly low in infants with PWS
and showed a steady decline between infancy and puberty. FSH levels were showed
the reverse pattern. Bone maturation ceased at approximately 13.9 years of
age. When hCG was administered, testosterone levels increase and reduced FSH
levels, however, testicular volume and inhibin B also remained low.
In conclusion, children with PWS
demonstrate a mixed form of central (hypothalamic (low LH levels)) and primary
(low inhibin B and high FSH levels) hypogonadism. This study suggests a flaw in
the Sertoli cell function or an early loss of sperm cell maturation. It has
been accepted that hCG promotes testosterone production and development of male