The story of the inhibin represents one of the major advances in our knowledge
of reproductive endocrinology in the past two decades. It represents an
excellent example of the power of clinical observation and investigation.
The original description of the pituitary cytological changes that followed
testicular irradiation, and their reversal by aqueous testicular extracts, remained
relatively unexplored until the advent of sensitive radioimmunoassays
for follicle-stimulating hormone (FSH) and their application to the study of
the endocrinology of male infertility. Several clinical investigators from all
over the world more or less simultaneously published their findings, that
many men with seminiferous tubule failure, leading to infertility, had
elevated serum FSH levels, while luteinising hormone (LH) and testosterone
often remained within the normal range for fertile controls. This gave rise
to the hypothesis that spermatogenic failure might lead to diminished secretion
of a seminiferous epithelium-related feedback factor, corresponding to
the activity originally found in testicular extracts. Deficiency of a possibly
related factor was postulated to account for the selectively elevated FSH
levels observed in women as menopause approached. Initial efforts to isolate
the active principle from testicular extracts proved to be fruitless, despite
confirmation of the ability of both testicular extracts and ovarian follicular
fluid to induce selective FSH suppression when administered in several
animal models. The demonstration by the late Paul Franchimont that seminal
plasma from normal men lowered FSH levels in castrate male rats, while
seminal plasma from men with severe seminiferous tubule failure did not,
was highly significant as a very early stimulus to the quest for inhibin.