The obligatory role of pituitary luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) in the control of testicular function
is well established. However there is increasing experimental evidence,
largely in the rat, that quantitatively normal spermatogenesis not only
requires an adequate local supply of testosterone but also the complex
interactions between the various cellular components within the
seminiferous tubules and interstitial compartments of the testis. The
critical role of paracrine mechanisms in the testis may be reflected by
the defective spermatogenesis in idiopathic male infertility where
systemic levels of LH, FSH and testosterone are normal or elevated.
Thus to further our understanding of the hormonal control of
spermatogenesis and to define possible aetiological mechanisms in the
infertile man, the study of paracrine mechanisms in the human testis is
of paramount importance.
The approach to study paracrine mechanisms in the human testis was
to establish in vitro techniques whereby individual components of the
testis were isolated and specific functional markers defined so that
their subsequent interaction could be further studied in vitro. At the
same time, the delineation of these 'local' parameters were related to
the overall functional states of the testis as defined by circulating
levels of LH, FSH, testosterone and the histological assessment of
Testes were obtained at orchidectomy for prostatic carcinoma.
Methods were established to examine the effect of intratesticular levels
of testosterone and systemic levels of LH, FSH and testosterone on
quantitative measures of spermatogenesis. For this purpose a simple
technique which involved enumeration of spermatid nuclei in fixed
testicular homogenates to determine daily sperm production was adopted.
Daily sperm production in this group of ageing testes was generally
lower than has been observed previously for younger men. Although
intratesticular levels of testosterone varied widely there was no
indication of an intratesticular deficiency of testosterone as a
critical factor in subnormal spermatogenesis in the ageing testis.
Inhibin, a peptide marker of Sertoli cell function was measured in
human testicular extracts by bio- and radioimmunoassay. The
relationship observed between FSH and both inhibin bioactivity and
immunoactivity imply that the role of inhibin in the testis may be
somewhat different to the classical concept of FSH feedback.
A technique for the routine isolation of human Leydig cells was
established. Human Leydig cells purified by Percoll density
centrifugation were highly responsive to hCG, although sensitivity and
receptor number were significantly lower compared to the rat. This
system was used to test for the effects of putative paracrine factors on
human Leydig cell function.
In conclusion, a number of in vitro techniques have been
established and validated which provide a basis for future investigation
of seminiferous tubule and Leydig cell function in the human testis.