Table 1.
Examples of studies employing genetic or pharmacological manipulations to disclose site-specific or cell-specific effects of leptin
| Reproductive phenotype | Ref. | |
|---|---|---|
| Global deletion/blockade | ||
| LepR in the brain | infertility, no pubertal development | 20 |
| LepR in the forebrain | infertility, no pubertal development | 22 |
| Ubiquitous melanocortin antagonism (Ay mouse) | abnormal estrous cyclicity | 35 |
| Melanocortin antagonism (pharmacology) | decreased steroid-induced LH surge; normal leptin effect on reproduction (ob/ob mice) | 36, 38 |
| MC4R deficiency | no deficits reported | 37 |
| NPY knockout | normal fertility | 44 |
| NPY knockout in ob/ob mouse | partial improvement of fertility | 44 |
| Cell-specific deletion | ||
| LepR from GnRH neurons | normal fertility, normal litter size | 22 |
| LepR from POMC neurons | normal fertility, normal litter size | 39 |
| LepR from AgRP/NPY neurons | normal fertility | 40 |
| LepR from AgRP/NPY and POMC neurons | normal fertility, normal litter size | 40 |
| LepR and InsR from POMC neurons | hyperandrogenism, ovarian abnormalities and fertility deficits | 41 |
| LepR from SF-1 neurons | normal fertility, normal litter size | 61, 62 |
| Site-specific reactivation | ||
| Exogenous LepR in the NTS | no rescue of fertility | 29 |
| Exogenous LepR in the Arc | improvement of cyclicity in Koletsky rats | 29 |
| Endogenous LepR in the Arc | no rescue of fertility | 54 |
The consequences of the manipulations for the animal reproductive function are summarized in the second column.