Endocrine Abstracts

Growth hormone (GH) is an important factor involved in the regulation of multiple biological functions. Although the influence of GH is widespread throughout several organs and tissues, the effects of GH on brain functions, such as those related to reproductive functions, are still elusive. GH deficiency or resistance can be related to late puberty onset, lack of sexual maturation and infertility. In contrast, GH therapy can accelerate puberty onset or be used to increase pregnancy rates in woman treating fertility-related problems. Thus, GH seems to modulate reproduction. However, the molecular and cellular mechanisms by which GH could potentially modulate the reproductive system are not fully understood. To understand whether GH signaling in the brain is required for sexual maturation and maintenance of reproductive functions, we used the Cre-LoxP technology to induce GH receptor (GHR) deletion in specific neuronal populations (kiss1-Cre or leptin receptor-Cre mice). Sexual maturation was assessed daily by determining the age and weight at the vaginal opening and at the first occurrence of vaginal cornification in the vaginal lavage (first estrus). These parameters were monitored daily until 80 days of age. Body weight was monitored weekly and at each specific stage of sexual maturation. The uterine mass and local fat pad mass were also determined in adult female mice. We observed that specific GHR deletion from Kiss1 expressing cells induced no effect on sexual maturation or body weight of female mice. In contrast, LepR GHR KO female exhibited delayed onset of first estrus, despite no changes on the age of vaginal opening or body weight at the specific stages of sexual maturation. However, LepR GHR KO female were lighter compare to the littermate controls throughout the development, suggesting that LepR GHR KO females need to reach a specific body weight before having sexual maturation. Accordingly, adipose fat pads weight was significantly reduced in adult LepR GHR KO females compared to control. Taking together, our results suggest that GHR expression on Kiss1 expressing cells is not required for puberty onset in female mice. However, growth hormone signaling on LepR expressing cells seems to regulate the puberty timing. Whether the observed effects on sexual maturation are dependent on body weight needs to be further investigated.