Search

The receptors and neurotransmitter pathways that may participate in the inhibitory action of 5-hydroxytryptamine (5HT) on prolactin release during late pregnancy and lactation in rats were studied. Administration of the 5HT synthesis inhibitor, p-chlorophenylalanine, to late pregnant rats induced a significant increase in serum prolactin concentrations at 17:00 h on day 19 of pregnancy that was partially blocked by injections of the 5HT precursor, 5-hydroxytryptophan, or the 5HT agonists, 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (S1a), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (S2) and N-(3-chlorophenyl)imidodicarbonimide diamide HCl (S3), but not by RU 24969 (S1b) or 1-meta-(chlorophenyl)-piperazine-2-HCl (S1a-2c). The 5HT neurotoxins, fenfluramine and p-chloroamphetamine, which selectively destroy fine axon serotoninergic fibres but not coarse ones, prevented the increase in circulating prolactin observed at 18:00 h on pro-oestrus and on day 21 of pregnancy, but did not modify serum prolactin concentrations at 17:00 h on day 19 of pregnancy. Administration of the adrenergic antagonists, metoprolol or prazosin, also prevented the stimulatory effects of p-chlorophenylalanine or ketanserin in pregnant rats on day 19 (17:00 h) or on days 10-12 (16:30 h) in lactating rats separated from their litters. Administration of p-chlorophenylalanine to pregnant rats on day 19 reduced dopamine concentrations in the arcuate nucleus and in the anterior hypothalamus and noradrenaline concentrations in the anterior hypothalamus and the suprachiasmatic nucleus. These results indicate that the inhibitory actions of 5HT on prolactin release in pregnant and lactating rats are mediated by S1a, S2a and S3 receptors and by the coarse axon serotoninergic fibres. In addition, the inhibitory actions of 5HT may modulate the action of a stimulatory adrenergic pathway, as well as the concentrations of noradrenaline and dopamine in different hypothalamic areas, which, in turn, particularly arcuate nucleus dopamine, regulate prolactin release.

Growth hormone (GH) concentrations were measured throughout pregnancy in rats. The effects of surgical stress, ovariectomy, and treatments with the antiprogesterone mifepristone (RU 486) or the antioestrogen tamoxifen on serum GH, progesterone and prolactin were studied. GH concentrations were low during the first 18 days of pregnancy, except on the morning of day 5, and increased progressively from day 19 reaching peak values on the mornings of days 21 and 22. Thereafter GH concentrations decreased progressively, reaching very low values at 24.00 h on day 22, in parallel with a rise in serum prolactin concentrations. Surgical stress, performed at 12.00 h on day 20 of pregnancy, diminished serum GH concentrations 10 min later, but these returned to values similar to those of the non-operated rats 1-24 h later. Surgical stress did not modify serum prolactin concentrations at any time. Ovariectomy performed on the morning of day 19 produced the expected fall in serum progesterone and a rise in prolactin which lasted until the night of day 20. Serum GH concentrations were significantly diminished with respect to controls on day 20 and the morning of day 21 and then increased. Treatment with mifepristone on day 19 produced a simultaneous rise in serum prolactin and a fall in serum progesterone and GH by 08.00 h on day 21. Treatment with tamoxifen on days 3 and 4, or given daily from day 17 onwards did not modify prolactin concentrations but diminished serum GH concentrations at 08.00 on day 5 and on days 19-22, with the exception of a peak on day 22 (08.00 h). Tamoxifen also decreased serum progesterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Suckling, starting at 19:00 h on Day 18 of pregnancy, induced a significant increase in serum prolactin concentration at 20:00 h on Day 19 of pregnancy, but no increase in mammary gland casein or lactose content. Mifepristone (2 mg/kg) injection at 08:00 h on Day 19 of pregnancy induced significant increases in casein, but not in lactose, 24 h after administration. Mifepristone alone did not induce prolactin secretion, indicating that lactogenesis was induced by placental lactogen in the absence of progesterone action. When mifepristone was injected into suckling rats, serum prolactin concentrations were higher than in the untreated suckling rats. Casein in these rats increased significantly 12 h after mifepristone administration and lactose at 24 h after. If the suckling mifepristone-treated rats were given two injections of bromocriptine (1.5 mg/kg) at 12:00 h on Days 18 and 19 of pregnancy, serum prolactin concentrations were not increased by suckling, but casein and lactose concentrations in the mammary gland showed values similar to those obtained in the mifepristone-treated non-suckling rats. Mifepristone can therefore potentiate suckling-induced prolactin release in pregnant rats, demonstrating a direct central inhibitory action of progesterone on prolactin secretion. This suckling-induced prolactin secretion, unable to induce casein or lactose synthesis in the presence of progesterone, enhanced significantly synthesis of these milk components in the absence of progesterone action (rats treated with mifepristone). Fatty acid synthase, which is stimulated by the suckling stimulus in lactating rats, was not modified by mifepristone or suckling in pregnant rats.

Administration of progesterone (5 or 10 mg) to pregnant rats increased serum prolactin significantly on the afternoon of Days 4, 6, 7 and 8 of pregnancy, but had no effect on later days. On Day 10 progesterone administration increased serum prolactin only in rats treated with oestrogen the day before. A similar treatment with oestrogen and progesterone was unable to stimulate secretion on the afternoon of Day 13 of pregnancy. In rats from which the corpora lutea had been unilaterally removed and hence endogenous progesterone levels were 50% of the normal values, or in those that carried 4 conceptuses, progesterone treatment after oestradiol priming was partly effective in inducing prolactin release on Day 13. However, in rats ovariectomized, with bilateral excision of the corpora lutea, or with 2 conceptuses left, treatment with ovarian steroids markedly increased serum prolactin values. By Day 13 all the rats from the ovariectomized group or with bilateral excision of the corpora lutea had aborted. On Day 13, therefore, the high serum concentrations of feto-placental factors and of progesterone are responsible for the blockade of the spontaneous and ovarian steroid-induced prolactin release. On the other hand, on Day 16 of pregnancy the decrease of circulating progesterone by excision of the corpora lutea or by ovariectomy followed by oestradiol treatment significantly increased serum prolactin on Day 17. Removal of all the conceptuses did not modify the effects of these treatments. The present results demonstrate different roles of progesterone upon the control of prolactin secretion. After a stimulatory action during the first days of pregnancy, there is a change to an inhibitory control at the end of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)