Targeted deletion of somatotroph insulin-like growth factor-I signaling in a cell-specific knockout mouse model.

The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I remain unclear. We have developed a cell-specific knockout mouse in which the IGF-I receptor was ablated from the somatotroph in order to validate and characterize IGF-I negative regulation; we termed this the somatotroph IGF-I receptor knockout (SIGFRKO) mouse. The SIGFRKO mice demonstrated increased GH gene expression and secretion as well as increased serum IGF-I.

Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines.

Kisspeptins, and their G-protein coupled receptor 54 (GPR54), are key components in the regulation of gonadotropin-releasing hormone (GnRH) secretion in humans and other mammals. Several studies demonstrate that the central or systemic administration of kisspeptin increases GnRH and gonadotropin secretion in both prepubertal and adult animals; however, the cellular targets and intracellular mechanisms of action in the central reproductive axis are unclear. In this study, we documented the presence of GPR54 in two GnRH secreting neuronal cell lines (GT1-7 and GN11).

Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1).

Mice lacking estrogen receptor alpha in the pituitary gonadotroph (PitEsr1KO) were generated to determine the physiologic role of pituitary estrogen signaling in the reproductive axis. PitEsr1KO female mice are subfertile or infertile and have elevated levels of serum luteinizing hormone (LH) and LH beta subunit gene expression, reflecting a lack of estrogen negative feedback effect on the gonadotroph. While serum LH values are elevated in PitEsr1KO mice, the degree of elevation is much less than that observed in ESR1-null mice, indicating that the hypothalamus must also have an important role in estrogen negative feedback.

Estrogen regulation of gene expression in GnRH neurons.

Estrogen plays an essential role in the regulation of the female reproductive hormone axis, and specifically is a major regulator of GnRH neuronal function in the female brain. GnRH neuronal cell lines were used to explore the direct effects of estradiol on gene expression in GnRH neurons. The presence of estrogen receptor (ER) binding sites was established by a receptor-binding assay, and estrogen receptor alpha and beta mRNA were identified in GN11 cells and ERbeta in GT1-7 cells using RT-PCR analysis of mRNA.