J. Rehman et al., Experimental hyperprolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms, INT J IMPOT, 12(1), 2000, pp. 23-32
Introduction: The purpose of this study was to induce hyperprolactinemia in
adult male rats and determine its effect on the central and peripheral med
iated neurogenic as well as myogenic mechanisms of erectile function/dysfun
ction in a rat model. The use of penile reflexes in awake animals was used
to test the effect of both central and peripheral mechanisms. Electrical st
imulation of the cavernous nervous was used to test peripheral neural funct
ion and intracorporal injection of papaverine was used to test the intactne
ss of the corporal smooth muscles. These mechanisms were further explored b
y administration of testosterone.
Methods: Eighteen Fisher-344 200-250 g rats aged 10 weeks were used in this
study. Group 1 (n = 6) hyperprolactinemia was induced with subcutaneous (S
Q) injection of 5 mg rat prolactin (NIDDK-r-PRL-B-7, biopotency 25 IU/mg) i
n two divided doses daily for 1 week. Testosterone propionate 100 mg/kg dis
solved in sesame oil was given intramuscularly on day 1 (weekly dose). Grou
p 2 (n = 6) control animals received SQ injection of vehicle twice daily an
d sesame oil I/M on day 1. Group 3 (n = 6) received testosterone propionate
. Penile reflexes (erections, cups, flips and clusters) were assessed prior
to induction ( x 3) of and following one-week state of hyperprolactinemia
(day 5, 6 and 7). All animals were trained three times before recording the
penile reflexes. The penile reflexes being averaged to give a single compo
site score for each animal. All animals underwent dissections that isolated
the cavernosal bodies and cavernosal nerves. Cavernous nerves were activat
ed and intracorporal pressures were recorded at increasing current magnitud
e (range 0.5-10 mA). Following that corporal smooth muscle reactivity was d
etermined by increasing injection of papaverine (100-3000 mu g). Concentrat
ion response curves (CRCs) were then generated by plotting percent change (
fractional change to make standardized comparison) to increasing neurostimu
lation or papaverine concentrations at half-log increments. Serum prolactin
was determined by rPRL radioimmunoassay Kit-Amersham while serum testoster
one was determined Testosterone ELISA Kit-Neogen.
Results: Penile reflexes were normal in all groups at the start of experime
nt but after 1 week of hyperprolactinemia, reflexes were totally abolished
in hyperprolactinemia rats (Group 1) and unchanged in Groups 2 and 3. Respo
nse to cavernous nerve activation and resulting rise in intracorporal press
ure to increasing current (range 0.5 - 10 mA) were statistically non-signif
icant in any groups. Similarly the intracorporal pressure response to pharm
acologic erection induced by papaverine (100-3000 mu g) were also non-stati
stically significant in any groups. Serum prolactin level in all rats recei
ving prolactin were > 500 ng/ml and the rat group receiving testosterone, s
erum level were > 20 x higher than the control rat.
Conclusions: This approach allowed more clear separation of central and per
ipheral mechanism of erection. This study shows a central neurological effe
ct of hyperprolactinemia on erectile function. Hypogonadism does not seem t
o contribute to the impaired penile reflexes as documented by replacement o
f testosterone did not recover the centrally mediated penile reflexes. Lowe
red serum testosterone is secondary phenomenon. These observations may have
important implications for the understanding, the mechanism and treatment
of men with hyperprolactinemia as well as future research in this field.