Gr. Aravindan et al., EFFECT OF ALTERING ENDOGENOUS GONADOTROPIN CONCENTRATIONS ON THE KINETICS OF TESTICULAR GERM-CELL TURNOVER IN THE BONNET MONKEY (MACACA-RADIATA), Journal of Endocrinology, 137(3), 1993, pp. 485
The role of FSH and diurnal testosterone rhythms in specific germ cell
transformations during spermatogenesis were investigated using DNA fl
ow cytometry and morphometry of the seminiferous epithelium of the adu
lt male bonnet monkey (Macaca radiata), the endogenous hormone levels
of which were altered by two different protocols. (1) Active immunizat
ion of five monkeys for 290 days using ovine FSH adsorbed on Alhydroge
l resulted in the neutralization of endogenous FSH, leaving the LH and
diurnal testosterone rhythms normal. (2) Desensitization of the pitui
tary gonadotrophs of ten monkeys by chronically infusing gonadotrophin
-releasing hormone analogue, buserelin (50 mug/day release rate), via
an Alzet pump implant (s.c.) led to a 60-80% reduction in LH and FSH a
s well as total abolition of testosterone rhythms. The basal testoster
one level (3.3 +/- 2.0 mug/l), however, was maintained in this group b
y way of an s.c. testosterone silicone elastomer implant. Both of the
treatments caused significant (P<0.01) nearly identical reduction in t
esticular biopsy scores, mitotic indices and daily sperm production ra
tes compared with respective controls. The germ cell DNA flow cytometr
ic profiles of the two treatment groups, however, were fundamentally d
ifferent from each other. The pituitary-desensitized group exhibited a
significant (P < 0.001) increase in 2C (spermatogonial) and decrease
in 1C (round spermatid) populations while S-phase (preleptotene sperma
tocytes) and 4C (primary spermatocytes) populations were normal, indic
ating an arrest in meiosis caused presumably by the lack of increment
in nocturnal serum testosterone. In contrast, in the FSH-immunized gro
up, at day 80 when the FSH deprivation was total, the primary block ap
peared to be at the conversion of spermatogonia (2C) to cells in S-pha
se and primary spermatocytes (4C reduced by >90%). In addition, at thi
s time, although the round spermatid (1C) population was reduced by 65
% (P<0.01) the elongate spermatid (HC) population showed an increase o
f 52% (P<0.05). This, taken together with the fact that sperm output i
n the ejaculate is reduced by 80%, suggests a blockade in spermiogenes
is and spermiation. Administration of booster injections of oFSH at ti
me-points at which the antibody titre was markedly low (at days 84 and
180) resulted in a transient resurgence in spermatogenesis (at day 18
0 and 228), and this again was blocked by day 290 when the FSH antibod
y titre increased. Although in the two treatment groups overall sperma
togenesis, as indicated by 1C:2C ratios, was significantly (P<0.01) re
duced, the mechanisms by which this was brought about appeared to be d
ifferent, suggesting that lack of FSH and testosterone (in particular
the nocturnal testosterone surge) affect germ cell transformation at d
ifferent foci.