Further investigation revealed that Foxg1-Cre is also active in the developing Rathke��s pouch but not the hypothalamus in this model, suggesting we had serendipitously generated a mouse model also lacking pituitary AR. Intriguingly, circulating testosterone concentrations in this mouse model are unaffected by AR ablation, an observation inconsistent with the currently accepted negative-feedback paradigm. In this study, we describe the detailed characterisation of this unique model, revealing previously unknown functions for androgen signalling in the male pituitary with implications for our understanding of the control of the male HPG axis. Estrogen signalling is thought to be responsible for a proportion of the feedback attributed to testosterone at the hypothalamus and pituitary, and estrogen receptor �� levels are shown to increase in some tissues when AR is ablated or downregulated, raising the possibility that increased or retained estrogen signalling could explain the lack of impact loss of AR has on circulating gonadotrophin levels. Production of testosterone by testicular Leydig cells is tightly regulated by the hypothalamic-pituitary- gonadal axis, forming a homeostatic negative feedback loop, but exactly how this is affected is not entirely understood. In this study we examined a mouse line with ablation of androgen receptor in the pituitary to empirically determine the role of pituitary androgen receptor in the control of male pituitary hormone production. Foxg1-Cre was active from fetal life and ablated androgen receptor in the pituitary. Surprisingly this resulted in no change in circulating testosterone levels, questioning the currently accepted paradigm of testosterone-mediated feedback at the level of the pituitary. Further to this observation, in this study we demonstrate that circulating gonadotrophin levels are unaffected by loss of pituitary AR, suggesting androgens do not mediate negative feedback on the HPG axis at the level of the pituitary in males. Instead, we show that pituitary AR is required for repression of prolactin production and release by the male pituitary. The Fingolimod majority of Cre Recombinase mouse lines target multiple tissues; as such empirical establishment of sites of targeting is an essential step in validating the utility of any given line as fit for purpose. Foxg1-Cre is active in the developing brain in the telencephalon, anterior optic vesicle, otic vesicle, facial and head ectoderm, olfactory epithelium, mid�Chindbrain junction, and pharyngeal pouches. Whilst these structures do not contribute towards the hypothalamus, Foxg1-Cre is active in Rathke��s pouch from e10 and previous studies use Foxg1-Cre to ablate a floxed gene of interest in the pituitary but not the hypothalamus. In addition, Foxg1-Cre is also expressed ectopically in some tissues outside of the brain, although the use of mice with 129SvJ and C57BL/6 BU 4061T clinical trial backgrounds is shown to limit this. We have ourselves previously used Foxg1-Cre to ablate androgen receptor action from the caput epididymal epithelium. In this case, the epididymal effects we observe were independently confirmed in a second model that did not have pituitary AR ablation, suggesting a localised impact of AR ablation at this distal site, with no impact on the central HPG axis.