Steroid Receptor Coactivator-1 Is Not Required for Androgen-Mediated Sexual Differentiation of Spinal Motoneurons

Abstract

Steroid receptor coactivator-1 (SRC-1) amplifies genomic steroid hormone signal transduction and has been implicated in steroid-mediated sexual differentiation of the mammalian nervous system. We investigated the possible effect of an SRC-1 null mutation on 2 morphological endpoints of androgenic signaling: the number and size of motoneurons within the spinal nucleus of the bulbocavernosus (SNB). In wild-type C57/BL6 mice, SRC-1 immunoreactive nuclei were observed within the SNB and one of its target muscles, the levator ani. However, SRC-1 null mice were indistinguishable from sex-matched wild-type littermates in both SNB number and cross-sectional area of SNB motoneurons. Similarly, we found no difference between SRC-1 null and wildtype littermates in the number or size of motoneurons in the retrodorsolateral nucleus, a motor pool that is not typically sexually differentiated in either number or size. These results demonstrate that SRC-1 is not essential for the development and maintenance of a sexually dimorphic neuromuscular system.

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

“…Similar observations have been made in white-footed mice (Forger and Breedlove, 1987), gerbils (Ulibarri et al, 1995), and several strains of Mus musculus (Wee and Clemens, 1987;Park et al, 2002;Monks et al, 2003;Zuloago et al, 2007). Larger somata likely reflect differences in electrophysiological properties, protein synthesis, and more robust dendritic organization, all of which are androgen sensitive in SNB motoneurons (see below).…”

“…Although SNB motoneurons express several steroid receptor coactivators (SRC-1, SCR-2, CBP, p300, cJUN), most other lumbar motoneurons, including those that do not respond morphologically to changes in androgen, also do (O'Bryant and Jordan, 2005). In addition, soma size of SNB motoneurons in SRC-1 knockout mice does not differ from that of wild-type controls (Monks et al, 2003). Thus, at this point, the molecular basis of the unusual androgen responsiveness of SNB motoneurons is not clear.…”

Inhibition of Steroid Receptor Coactivator-1 Blocks Estrogen and Androgen Action on Male Sex Behavior and Associated Brain Plasticity

“…Another study, however, demonstrated a profound inhibition of lordosis in female rats treated with SRC-1 antisense (Apostolakis et al, 2002). Studies of SRC-1 knock-out mice also found no effect on the development of the androgen-dependent motoneurons within the spinal nucleus of the bulbocavernosus (Monks et al, 2003), suggesting that this cofactor may not be important for androgendependent neuroendocrine processes. The present study clearly indicates that SRC-1 alone is important for the activational effects of testosterone on many aspects of male-typical sexual behaviors (Figs.…”

Hypothalamic progesterone receptor-A mediates gonadotropin surges, self priming and receptivity in estrogen-primed female mice

“…Coincident with receptivity is a period of time when females exhibit a series of 'courtship' behaviors that foster behavioral interactions with the males and facilitate the electrophysiological properties of the neurons in the female hypothalamus. It is likely that these behaviors, while not reflex, are due to hormonal modulation of the serial neurocircuitry via ER (Pfaff & Schwartz-Giblin 1998), inducible PR (Monks et al 2001), and at least SRC-1 (Monks et al 2003). To verify this, the incidence of proceptive behaviors by the females was quantified.…”