Abstract:
The intention of this study was to investigate if prolactin had
an influence on the epididymis, a region of the male reproductive
tract concerned with the functional development of the sperm. The
epididymis helps sperm acquire the characteristics of motility
and fertilizing ability. This is made possible by the special
milieu in which the sperm are bathed while being nurtured within
the duct. The composition of this milieu is further dependent on
the secretory and absorptive nature of the epididymal epithelium.
The nature of the epididymal epithelium is in turn dependent on
several factors, both hormonal and non-hormonal. Thus, it seems
that one big cascade of events is involved, that finally
culminates in the production of functionally developed sperm.
The crux of the problem was to first select an appropriate
parameter to assess the functional status of the epididymis and
then identify the various factors that influence it. The next
step was to investigate if prolactin had a role to play. Sialic
acid was one of the parameters that was chosen. Although there is
yet no clear appreciation of the significance of sialic acid for
sperm function, there is evidence to suggest that the epididymis
synthesizes this compound. Experiments involving sham-operated,
duct ligated and orchidectomised animals clearly showed that the
sialic acid derived from testis could significantly contribute to
the levels in the epididymis. Nevertheless, the presence of
sialic acid in epididymis even after efferent duct ligation and
the higher levels of this compound in cauda than in the caput
made it amply clear that the epididymis is capable of
synthesizing sialic acid. Moreover, these studies also showed
that factors derived from testicular fluid including androgens
controlled sialic acid level in the epididymis.
A simple way to see if prolactin is involved is to inject
prolactin in animals from an exogenous source (as practised by
other investigators) and then look for the impact on the
epididymis. But then, it was inferred from the preceeding
experiment that several factors of testicular origin affect
sialic acid level in the epididymis. For this reason, prolactin
treatment in intact rats was not preferred. The choice now was to
use efferent . duct ligated or orchidectomised animals for
prolactin treatment because all components of testicular origin
could be kept away. Accordingly, when prolactin was
administered at various doses, the epididymis of orchidectomised
and not the duct ligated animals responded to prolactin
treatment. The following explanations could be offered. Efferent
duct ligation prevents the testicular fluid and spermatozoa from
reaching the epididymis but maintains the availability of
androgens through general circulation. Orchidectomy, on the
otherhand, involves the removal of the primary source of
androgens together with all testicular factors known to influence
epididymal function. Since the androgens continue to reach the
epididymis in duct ligated animals and the epididymis is
predominantly an androgen dependent organ, it has been proposed
that the action of prolactin is perhaps masked by the much
greater effects of androgens in the tissue. In view of these
results it was clear that orchidectomised animals would be the
most appropriate model to study the effect of prolactin in the
epididymis.
Prolactin treatment to orchidectomised rats increased the sialic
acid levels in a dose dependent manner. It had been suggested
that prolactin directly influences the epididymal sialic acid,
perhaps at the level of synthesis. The experiment when repeated
with bromocryptine treatment (an ergot alkaloid that reduces
circulating levels of prolactin) to orchidectomised rats
confirmed that prolactin was involved. It was also clarified that
prolactin does not interfere with the assay of sialic acid.
The activity of two representative glycosidases was used as yet
another parameter to monitor the effoct of prolactin on the
epididymis. In this case, the response although positive, was
not exactly dose related, implicating that different parameters
need not necessarily respond alike to tho samo treatment. It has
11
been suggested that the activity of glycosidases measured may
represent the net result of an interaction between steroid
(androgen) and protein (prolactin) hormone action at each dose of
prolactin treatment.
In order to see how long the injected prolactin remains in
circulation, the circadian pattern of serum prolactin bioactivity
in orchidectomised animals given various doses of prolactin
injection was determined. It appeared that the half life of
injected prolactin was small, perhaps less than 15 min. In
addition, a rebounding phenomenon was observed.
In the first two Chapters prolactin was shown to influence
biochemical parameters like the sialic acid and the activity of
glycosidases in the epididymis. However, the impact of prolactin
on the structure of the epididymal epithelium particularly the
principal cells, was not known. For this purpose, both light and
electron microscopic studies were performed. From the light
microscopic studies it was clear that prolactin had a positive
effect on the epididymal epithelium but had no influence on the
muscular layer. Electron microscopic studies revealed that
prolactin profoundly influenced the ultrastructure of the
principal cell. Orchidectomy induced atrophic changes and
prolactin treatment to these animals brought about rejuvenation.
Thus, prolactin was shown to have a trophic action in the
epididymis.