Table 1.
Characteristics of polycystic ovary syndrome (PCOS) and alterations in the neuroendocrine axis in preclinical PCOS animal models.
| Parameter | Prenatally Androgenized Animals (PNA) | Postnatally Androgenized Animals | Letrozole Treated Animals | Clinical Data |
|---|---|---|---|---|
| Hyperandrogenemia | Mouse—Yes | Mouse, Rat—High dihydrotestosterone (DHT) due to exogenous DHT treatment, but no increase in testosterone (T) | Mouse—Yes | Yes (60% according to the Rotterdam criteria) |
| Rat—Yes | Rat—Yes | |||
| Sheep—Yes | - | - | ||
| Monkey—Yes | - | - | ||
| Luteinizing hormone (LH) levels | Mouse—High + ↑pulse frequency | Mouse—No change | Mouse—High | High LH pulse frequency and amplitude |
| Rat—High + ↑pulse frequency | Rat—No data | Rat—High | ||
| Sheep—↑↓ (Conflicting reports) | - | - | - | |
| Monkey—High | - | - | - | |
| Negative feedback | Mouse—Impaired | Mouse—No data | Mouse—No data | Need higher doses of Estradiol and progesterone to decrease LH to similar levels in healthy women |
| Rat—No data | Rat—No data | Rat—No data | ||
| Sheep—Impaired | - | - | ||
| Monkey—Impaired | - | - | ||
| GnRH/GnRH neurons | Mouse (PNA)—↑GnRH firing rate; ↑GABAergic inputs to GnRH neurons; ↑GABAergic postsynaptic currents Mouse (PAMH)—↑GnRH firing rate; ↑GABAergic inputs to GnRH neurons | Mouse—No data | Mouse—No data | No data |
| Rat—No data | Rat—No data | Rat—No data | ||
| Sheep—No data | - | - | ||
| Monkey—No data | - | - | ||
| Kisspeptin/Kisspeptin neurons | Mouse—No data | Mouse—No data | Mouse—No data | Positive correlation between kisspeptin and LH levels; NK3R antagonist treatment decreased LH and T levels in women with PCOS |
| Rat—↑Kiss and NKB positive cells in ARN; ↑Kiss1 and Tac2 mRNA levels | Rat—↓Kiss1 mRNA in the hypothalamus ↓Kiss-ir cells in ARN | Rat—↑ARN Kiss cells | ||
| Sheep—No change Kiss cells, but ↑ in cell size of ARN Kiss cells; ↓excitatory glutamatergic inputs to Kiss cells | - | - | ||
| Monkey—No data | - | - | ||
| GABA/GABA neurons | Mouse—↑GABAergic inputs from ARN to GnRH neurons; ↓Progesterone receptor in ARN GABA neurons | Mouse—No data | Mouse—No data | Increased GABA in CSF of PCOS women |
| Rat—No data | Rat—No data | Rat (LET by oral gavage)—↓GABA mRNA levels in several brain regions including the hypothalamus; Co-administration of GABA with LET decreased T levels and body weight | ||
| Sheep—No data | - | - | ||
| Monkey—No data | - | - |