ABSTRACT
The effect of drug-induced hypo- and hyperprolactinaemia on pituitary gonadotrophin releasing hormone receptors (GnRH-R), serum and pituitary gonadotrophins (LH and FSH) and prolactin was investigated in intact adult male and female rats. Hypoprolactinaemia (serum prolactin <20% of control values) resulting from dopamine agonist (bromocriptine) infusion (4 mg/kg per day for 7 days) was accompanied by a 40–50% increase in GnRH-R in both male and female animals, though this was not accompanied by any major change in serum or pituitary LH and FSH. Hyperprolactinaemia (serum prolactin greater than ten times control values) induced by the dopamine receptor antagonist metoclopramide (65 mg/kg per day for 7 days) increased GnRH-R between 35 and 45% in both male and female rats without altering serum gonadotrophins. Domperidone (1 mg twice daily for 14 days) also increased GnRH-R by 50% but only in female rats. Both dopamine antagonists significantly increased pituitary prolactin content. Pituitary FSH increased in female rats treated with both metoclopramide and domperidone.
The stimulatory effects of bromocriptine and metoclopramide on GnRH-R in male rats were prevented by concurrent treatment with a GnRH antiserum, suggesting that the drug effects were mediated through alteration in endogenous GnRH secretion.
Induction of massive (serum prolactin > 2000 μg/l) hyperprolactinaemia in male and female rats with a transplantable prolactin-secreting pituitary tumour did not reduce GnRH-R concentration, although serum gonadotrophins were suppressed and pituitary gonadotrophin content was increased.
These results indicate a dissociation between serum prolactin concentrations and pituitary GnRH receptor content and indicate that dopamine agonist and antagonist agents can influence GnRH-R independently of prolactin, possibly by acting on central dopamine receptors responsible for catecholaminergic regulation of GnRH secretion.
J. Endocr. (1984) 102, 215–223
RELATIONSHIP BETWEEN DURATION OF URETHANE OR PENTOBARBITONE ANAESTHESIA IN MALE AND FEMALE RATS AND ADENOHYPOPHYSEAL RESPONSE TO LUTEINISING HORMONE-RELEASING HORMONE
