Effect of manipulating central catecholamines on puberty and the surge of luteinizing hormone and gonadotropin releasing hormone induced by pregnant mare serum gonadotropin in female rats

Abstract

We have investigated the effect of manipulating central catecholamines on the timing of puberty (as assessed by vaginal opening) in female rats and the surge of luteinizing hormone (LH) and gonadotropin releasing hormone (GnRH) induced by pregnant mare serum gonadotropin (PMSG) in immature female rats. Manipulation of the catecholamines was carried out with either 6-hydroxydopamine (6-OHDA) administered with or without either desipramine (DMI) or pargyline, or α-methyl-p-tyrosine (α-MPT). The neonatal administration of 6-OHDA delayed puberty, an effect which was potentiated by pretreatment with DMI and was associated with a reduction in the rate of body growth. Catecholamine fluorescence in animals aged 60–65 days that had been treated with DMI followed by 6-OHDA was diminished only in the caudatus-putamen; treatment with 6-OHDA alone resulted in diminished fluorescence in the hypothalamus and in the intermediate but not the external layer of the median eminence. The neonatal administration of α-MPT had no significant effect on either the growth rate or the timing of puberty. Regular oestrous cycles occured after puberty in animals treated with either 6-OHDA or α-MPT. The PMSG-induced LH surge was significantly enhanced by 6-OHDA (administered i.v.) plus DMI, and reduced by 6-OHDA injected into the lateral ventricle (v). The inhibitory effect of 6-OHDA (v) wasreduced by DMI, but in animals given 6-OHDA (i.v.) after pargyline there was a marked reduction in the height of the LH surge. There was a good correlation between the changes in the concentrations of LH in peripheral plasma and the concentrations of GnRH in pituitary stalk plasma in that the PMSG-induced surge of GnRH was significantly increased by 6-OHDA (i.v.) plus DMI and reduced by 6-OHDA (v). In animals treated with 6-OHDA (i.v.) plus DMI catecholamine fluorescence was reduced only in the external layer of the median eminence, while after 6-OHDA (v) plus DMI degeneration was seen in the medial forebrain bundle. These results demonstrate a marked difference between the long-term and acute effects of 6-OHDA on the gonadotropin control system. Neonatal treatment with 6-OHDA plus DMI significantly delays puberty and the rate of body growth, but does not affect cyclical gonadotropin release and has no persistent effect on the hypothalamic catecholaminergic systems. The acute administration of 6-OHDA, depending upon the route of administration and whether it is given after DMI, can either potentiate or inhibit the PMSG-induced surge of GnRH and consequently LH by mechanisms which involve destruction, respectively, of either dopaminergic terminals in the median eminence or catecholaminergic fibres in the dorsal hypothalamus.