**6. Impact of ablation of LEPR in gonadotropes on other pituitary cell types**

The loss of leptin receptors in gonadotropes also had a broader impact on pituitary function. We reported a profound reduction in serum GH, in both mutant males and females (**Figure 3**) [1]. This reduction would expect to result in growth hormone deficiency, which, in our other models has resulted in significant changes in body weight (adult-onset obesity) [22]. However, when mice were weighed regularly for nearly a year, these deletion mutant animals grew normally and did not gain more weight than normal mice during their first year of life [1]. In addition, male mutants show reduced levels of serum TSH and prolactin [1]. There were also sex-specific differences in mRNA levels. As stated earlier, in deletion mutant females, *Fshb* and activin were reduced. In contrast, male deletion mutants showed reduced mRNA levels of *Fshb, Cga, Gh,* and *Ghrhr.* This phenotype may be the result of deficits in the production of paracrine factors from gonadotropes, which are needed to regulate the function of these cell types. Alternatively, we hypothesized that this phenotype may simply result from of the loss of multihormonal function in subsets of gonadotropes themselves. Evidence for the presence of multihormonal gonadotropes is reviewed in the next few paragraphs.

The presence of multihormonal gonadotropes in the rodent pituitary cell population is not unexpected since our group previously reported cells that stored gonadotropins

### **Figure 3.**

*Mutants lacking Lepr exon 17 in gonadotropes show significantly reduced levels of serum GH. This colored figure has not been published elsewhere. However, the data were published as separate figures (separating sexes) in ref. [1] in a completely different, black and white graph.*
