Androgens in Health and Disease.pdf - E Library

92 Lindzey and Korach
estrogen signaling paths may suffice to organize and activate some degree of mounting
behavior. Interestingly, a recent study by the same group compared behaviors of
αERKO, βERKO, and double knockout (α,βERKO males) (27). This study suggests
that whereas βERKO males exhibit a normal repertoire of mounting and copulatory
behaviors, the α,βERKO males exhibit even more severe deficits in mounting behaviors
than do the αERKO males. The implication is that ERβ may suffice to organize
or activate some degree of mounting behavior in the absence of ERα and that the
absence of both creates a more severe behavioral phenotype (27). The authors suggest
that ERα and ERβ may be somewhat redundant in their actions on mounting behaviors.
Nonetheless, in general, these data support the hypothesis that aromatization is necessary
for a normal suite of male sex behaviors and that E 2 acts primarily through ERα
to mediate the organization and/or activation of sex behaviors. By comparison, ERβ
apparently plays little role in male-typical sex behaviors. This generalization, however,
should be further tested in other species as ERα- and ERβ-specific agonists and
antagonists become available.
Androgen-dependent, intermale aggression is another behavior that has been reported
to depend on aromatization of T. Indeed, in a “resident–intruder” design, ARKO residents
exhibited no aggressive interactions against an ARKO intruder and wild-type (WT) resident
males also exhibited reduced aggression against ARKO intruders compared with
WT intruders (31). Neonatal E 2 treatments of ARKO males resulted in a dose-dependent
increase in intermale aggression that was most pronounced when E 2 treatments were
begun on neonatal day 1 and continued episodically through testing as adults. These data
suggest a critical window for organization of E 2 effects but because of experimental
design, they fail to distinguish between “organizational” and “activational” effects of E 2
on aggression. Although aggressive behaviors are normal in βERKO males, αERKO and
α,βERKO males both exhibit severe deficits in aggressive behaviors toward bulbectomized
intruders (27,29). Thus, E 2 and ERα are obviously critical to the normal
display of intermale aggression in mice and ERβ does not exert any redundant control
over aggression as it may for mounting behaviors (27).
HORMONES
The neural centers that regulate gonadotropin-releasing hormone (GnRH) synthesis
and secretion and, ultimately, secretion of gonadotropins are subject to organizational
and activational effects of T. Typically, luteinizing hormone (LH) secretion is
described as a “tonic” pulsatile background against which a “surge” component can be
overlaid. Both males and females possess “tonic” components, whereas only females
typically exhibit an estrogen-dependent, preovulatory LH “surge.” In some species,
such as primates, the ability to “surge” is not sexually differentiated; both the male and
female can deliver an LH surge when given the appropriate E 2 treatments. However,
in rodents, the ability to deliver an LH surge is sexually dimorphic and one region
implicated in sexual differentiation of the LH surge is the anteroventral periventricular
nucleus (AvPV). In female rodents, this region is larger, contains more dopaminergic
neurons and, furthermore, AvPV lesions abolish LH surges (32,33). Masculinization
by neonatal T treatments results in a male-typical AvPV characterized by reduced
volume and tyrosine hydroxylase (TH) immunostaining. Although no studies have
reported on AvPV nuclei of ARKO mice, analyses of αERKO mice demonstrated that
male αERKOs possess an AvPV more typical of female mice—larger and greater