Possible involvement of hypothalamic adrenaline in the sexually differentiated response of LH to an oestrogen stimulus in immature rats

Abstract

In the adult rats an increase in adrenergic activity in the medial preoptic area (MPOA) and the mediobasal hypothalamus (MBH) occurs during the proestrous ’critical period’ preceding the preovulatory gonadotrophin (LH) surge. Similarly, using adult rats ovariectomized in the morning of dioestrus and injected (s.c.) immediately with oestrogen (OEg) it was found that adrenergic activity increased in the MBH but not the MPOA during the expected ’critical period’. It was suggested from these observations that an oestrogen stimulated increase in adrenergic activity in the MBH might be concerned with the surge output of gonadotrophin. In a previously reported ontological study of an oestrogen stimulated output of gonadotrophin, it was found that the occurrence of this neurohumoral event was critically related to the age and sex of the animal. An injection (s.c.) of oestrogen at noon (day 1) in infant rats at as early an age as 21 days could elicit a surge of prolactin at 1800h the next day (day 2) and again on day 3; while a surge of LH occurred only at 1800h on day 3. Similar treatment of males at any age had no such effect. The purpose of the studies presented in this thesis was to investigate the development of central adrenergic systems concerned with the ontogeny and sexually differentiated output of gonadotrophin in response to an oestrogen stimulus in the infant rats. Adrenaline concentration and the activity of its synthesizing enzyme (phenylethanolamine-N-methyl transferase, PNMT) present in the MPOA and MBH of oestrogen treated 16--22-day-old females and 22-day-old males were measured. This showed that adrenaline concentration and activity of PNMT in the MBH of oestrogen treated 22-day-old female rats increase significantly (P<0.01) at 1600h both on days 2 and 3, 2h before the oestrogen dependent surge output of gonadotrophins (i.e. prolactin with or without LH) reach peak levels (1800h). Such an effect was not seen in similarly treated 16-day-old female and in 22-day-old male rats on day 3, with the exception of PNMT activity in 22-dayold males which showed an increase similar in the female. 22-dayold oil-treated male rats also showed an increase in PNMT in the MBH at 1600h which was not significantly different from those of oestrogen-treated rats. Noradrenaline and dopamine concentrations in the MBH of oestrogen treated 22-day-old female rats remained at baseline levels on days 2 and 3. In contrast to the MBH, the MPOA of these rats did not show an increase in either adrenaline concentration or PNMT activity on day 3. Subsequent measurements of PNMT activity in the MBH of oestrogen treated 22-day-old female rats at 4 hourly intervals throughout the days 2 and 3 showed the presence of a clear circadian rhythm with peak levels occurring at 1600h. This rhythm appears to be dependant on the presence of plasma oestrogen and glucocorticoids since oil-treated or adrenalectomized 22-day-old females did not show an increase in PNMT at 1600h. In conclusion, it is clear that an increase in adrenaline concentration in the MBH of oestrogen treated 22-day-old female rats appears to be in synchrony with an increase in its synthesizing enzyme, PNMT. Furthermore, it is temporally related to surge output of gonadotrophins (LH and prolactin) which occur 2h later (1800h). Whether or not the temporal relationship occurring in the oestrogen-treated 22-day-old females is directly concerned with the output of gonadotrophins, or with other hormones which increase at the same time, is a question which requires investigation.