Serotonin-reinstatement of luteinizing hormone surges after loss of positive feedback in ovariectomized rats bearing subcutaneous capsules containing oestrogen

Abstract

In ovariectomized rats treated chronically with oestrogen there is a loss of positive feedback effects on LH secretion. This was not due to depletion of pituitary LH since injection of LH releasing hormone (LH-RH; 50ng/100g body wt) caused a significant (P < 0\ m=. \ 01) rise in serum LH even after the loss of spontaneous LH surges. However, the magnitude of the increase in serum LH in response to LH-RH was greater (412 \m=+-\ 41 \g=m\g/l) before than after (291 \m=+-\ 29 \g=m\g/l) loss of the LH surges. Excessive blood sampling was also not responsible, since positive feedback responses declined comparably in rats bled daily or once every 3\p=n-\4 days.Progesterone (0\m=.\5mg s.c.), administered for 5 consecutive days, failed to restore LH surges indicating that deficiency of this steroid after ovariectomy does not cause positive feedback responses to disappear in rats exposed chronically to oestrogen. Moreover regular daily fluctuations in serum progesterone, probably of adrenal origin, occurred before as well as after daily LH surges were lost.Serotonin content and turnover were depressed (P < 0\ m=. \ 05) when ovariectomized rats first received the subcutaneous capsules containing oestrogen. This change correlated temporally with the onset of daily LH surges and was eventually lost. After 30 days exposure to oestrogen, serotonin turnover increased (P < 0\m=.\01) and positive feedback responses were absent. Catecholamine levels and turnover did not show differential responses to oestrogen and were depressed after acute as well as chronic steroid treatment.p-Chlorophenylalanine (pCPA; 250 mg/kg)+ l-dihydroxyphenylalanine (l-DOPA; 200 mg/kg), which depress serotonin and enhance catecholamine synthesis respectively, failed to reinstate LH surges, but these were restored in 22% of the rats receiving l-DOPA alone. pCPA, followed 2 days later by 5-hydroxytryptophan (5-HTP) at 11.00 h, reinstated LH surges in 88% of rats, and a dose\p=n-\response curve showed that as little as 4 mg 5-HTP/kg stimulated repetitive LH surges when given with pCPA according to this schedule.However, the administration of \g=a\-methyl-p-tyrosine + l-DOPA, an analogous treatment involving catecholamines, was only marginally effective (15%).These findings suggest that perturbations of monoamine metabolism occurring in ovariectomized rats exposed to oestrogen for several weeks contribute to loss of daily LH surges. Since pCPA + 5-HTP restored LH surges most effectively, then positive feedback may disappear as the facilitatory effect of serotonin is lost after chronic oestrogen administration.

Inhibition of Proestrous LH Surge and Ovulation in Rats Evoked by Stimulation of the Medial Raphe Nucleus Involves a GABA-Mediated Mechanism

“…possibly because of a blockade of its re lease [25]. However, they conflict with the results showing that 5-HT exerts a facilitatory role on the mechanisms controlling ovulation and gonadotropin secretion [9,10,17,19,30,31,51]. The mechanisms underlying these two opposite effects of se rotonin on LH secretion have not been completely established although antagonist responses have been evoked from the dor sal and medial raphe nuclei [33].…”

Dopamine Antagonist Speeds Up Tail Regeneration in Lizards Exposed to Continuous Darkness: Evidence for Prolactin Involvement

“…it has been demonstrated that the pineal organ is the principal site of extraretinal photoreception in Hemidactylus since both pinealectomy and light deprivation to the pineal abolished the stimulatory influence of increasing lengths of light and significantly retarded the regeneration process (44) and exogenous PRL stimulated tail regeneration in intact but not pinealectomized lizards exposed to continuous darkness, suggested that the pineal is somehow linked with the favorable influence of light on tail regeneration in lacertilians (4). In our recent investigations, p-CPA, an inhibitor of tryptophan hydroxylase (45,46) and an agent employed for chemical pinealectomy. retarded tail regeneration in animals exposed to 24:O LD, indicating that lizards with physically intact pineals but deprived of their ability to synthesize 5-HT do not exhibit the favorable influences of light on tail regeneration in lizards (47).…”

Serotonergic Mediation of a Negative Feedback Effect of Estrogen on Luteinizing Hormone Release in Ovariectomized Rats*

“…Estrogen is involved in stimulatory as well as inhibitory feedback control of LH release. 5HT has been implicated in mediation of the LH surge as well (23,24). It seems likely that estrogen acts through different mechanisms to inhibit pulsatile LH release and to sensitize or activate pathways stimulatory to the release of LH such as those involved in triggering the LH surge.…”