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We studied the capacity of different GH preparations, natural human (h)GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1.5 mg/kg) immediately after surgery (OVX-HYS-BC). The hormones were given at doses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and hGH, rhGH and 0.25 mg oGH, and lactose by both doses of oPRL, rhGH and 0.25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0.25 and 0.5 mg) or rhGH-treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0.5 mg rhGH induced levels of milk production similar to controls except on day 3. oPRL and rhGH (0.25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of 125I-labelled oPRL binding to crude liver membranes, was comparable with that of oPRL. While rhGH was ten times less active than oPRL, rPRL was 100 times lower and all the other GH preparations had at least 10(4) times lower capacity to displace 125I-labelled oPRL.(ABSTRACT TRUNCATED AT 400 WORDS)

The part played by the adrenergic system on the release of prolactin and lactogenesis induced by prostaglandin F2 alpha and the antiprogesterone RU 486 was studied in pregnant rats. Two doses of prostaglandin F2 alpha (150 micrograms) administered at 08.00 and 12.00 h on day 19 of pregnancy induced, at 12.00 h on day 20 (24 h after administration), a significant increase in the serum concentration of prolactin, with a significant decrease in serum progesterone levels. These hormonal changes significantly augmented casein and lactose levels in the mammary gland. Treatment with RU 486 (2 mg/kg) at 08.00 h on day 19 augmented casein and lactose concentrations in the mammary gland at 12.00 h on day 20 without modifying serum concentrations of prolactin and progesterone. The adrenergic antagonists, propranolol (3 mg/kg), metoprolol (10 mg/kg), ICI 118,551 (200 micrograms/kg), idazoxan (100 micrograms/kg) and prazosin (10 mg/kg), were administered s.c. at 12.00 and 20.00 h on day 19 and 08.00 h on day 20 of pregnancy to intact rats or to rats previously treated with RU 486 or prostaglandin F2 alpha. These adrenergic antagonists did not modify serum prolactin or progesterone levels in intact or RU 486-treated rats, but serum prolactin levels in the prostaglandin F2 alpha-treated group were significantly reduced by treatment with propranolol, metoprolol or prazosin. In addition, propranolol and ICI 118,551 also decreased the casein and lactose concentrations in the mammary glands of RU 486- and prostaglandin F2 alpha-treated rats, while the other compounds had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of para-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, on prolactin release was studied in rats on the day of pro-oestrus and at the end of pregnancy (day 19). The surges of prolactin normally seen in the afternoon of pro-oestrus in intact rats and in rats ovariectomized on dioestrous day 2 and primed with oestrogen were significantly inhibited by pCPA treatment. Administration of 5-hydroxytryptophan reversed the inhibitory action of pCPA on prolactin release. Treatment with progesterone also completely reversed the inhibitory effect of pCPA on prolactin release in pro-oestrous rats and partially reversed it in ovariectomized oestrogen-treated rats. Ovariectomy on day 19 of pregnancy induced a significant release of prolactin 12 and 24 h later. Administration of pCPA on day 18 of pregnancy produced a marked increase in serum concentrations of prolactin on days 19 and 20 in rats left intact or ovariectomized on day 19. Administration of 5-hydroxytryptophan significantly reversed this stimulatory effect of pCPA on prolactin release but did not modify the release of prolactin induced by ovariectomy. Methiothepin (1-[10,11-dihydro-8-(methylthio) less than b,f greater than thiepin-10,41]-4-methylpiperazine maleate), a serotonin receptor blocker, also induced a significant increase in serum concentrations of prolactin on day 20 of pregnancy in rats left intact or ovariectomized on day 19. These results suggest the existence of different serotoninergic actions in the regulation of prolactin release at pro-oestrus and in late pregnancy. Serotonin facilitates the surges of serum prolactin released at pro-oestrus and in ovariectomized rats treated with oestrogen; progesterone enhances this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously found that modifications to serum progesterone concentration have profound inhibitory effects on prolactin release in response to ether stress. The objective of the present study was to determine the effect of ether stress on progesterone secretion and the role of this steroid in ether-induced prolactin release. Serum progesterone concentration, 5 min after ether stress had been applied over a 2-min period, was consistently increased in male rats, in cyclic rats on the mornings of pro-oestrus and oestrus, and in androgenized rats in permanent oestrus. Ovariectomized androgenized rats showed the same response. Adrenalectomy of male and female rats abolished the progesterone increase induced by stress. Thus, the progesterone secreted by stressed rats is mostly of adrenal origin. In groups of male and pro-oestrous rats, circulating concentrations of prolactin and progesterone were measured from 5 to 60 min after stress. In both sexes the serum prolactin concentration was significantly increased at only 5 and 10 min after stress when compared with control values. In pro-oestrous rats the serum progesterone concentration was significantly higher than in controls at 5, 10 and 20 min after stress, whilst in male rats the concentration remained significantly higher at 30 min. Thirty minutes after the first stress, male and proestrous rats were etherized for 2 min, and bled 5 min after removal from the ether container. In female rats this second stress produced only a slight but significant increase in serum prolactin concentrations, whereas in male rats prolactin concentrations did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)

The serotoninergic regulation of prolactin release was studied in female rats in different reproductive states using ketanserin, a specific S2 receptor blocker, ICS 205-930 ((3 alpha-tropanyl)1H-indol-3-carboxylic acid ester), a specific S3 receptor blocker and p-chlorophenylalanine (pCPA), a serotonin synthesis inhibitor. Administration of ketanserin to pro-oestrous rats inhibited the afternoon prolactin surge; this inhibition was prevented by progesterone. On day 3 of pregnancy, pCPA or ketanserin blocked the afternoon prolactin surge, and administration of oestrogen (on day 2) and progesterone (on day 3) in combination, but not alone, prevented this effect. On day 9 of pregnancy, treatment with oestrogen (on day 8) and progesterone (on day 9) induced an afternoon surge of prolactin which was prevented by administration of ketanserin or pCPA. On days 9 and 16, pCPA induced a slight increase in serum prolactin in rats not treated with steroids, but ketanserin had no effect. On day 13, ketanserin and pCPA had no effect on serum prolactin levels, but after increasing serotoninergic transmission by injecting fluoxetine and 5-hydroxytryptophan, serum prolactin levels were decreased. On day 19, ketanserin produced a transient increase in the serum concentration of prolactin, probably produced by the marked decrease in the serum concentration of progesterone induced by the S2 receptor blocker. Administration of ICS 205-930 to pro-oestrous rats or rats on day 19 of pregnancy had no effect on serum concentrations of prolactin and progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Ether stress applied at 10.00 h induced a 100% increase in serum prolactin in intact and ovariectomized androgenized rats. Ovariectomy significantly diminished the basal serum prolactin values observed in intact androgenized rats. Two doses of progesterone (5 mg) given to intact and ovariectomized androgenized rats 14 and 2 h before exposure to ether stress increased prolactin values in the control groups but completely prevented the effect of stress. Exposure to ether stress induced a 100% increase in serum prolactin values in androgenized rats with increased serum progesterone levels 4 days after the induction of ovulation and the luteal phase with human chorionic gonadotropin (hCG). A group of androgenized rats with induced maternal behaviour and which had been suckled for 6 days was given 100 i.u. hCG and suckled for another 6 days after the hCG-induced luteal phase had been established. The serum prolactin and progesterone values of these rats were significantly higher than those treated with hCG only and ether stress did not increase prolactin release. A greatly increased serum concentration of prolactin was obtained in pro-oestrous and oestrous virgin rats after exposure to ether stress. Serum prolactin was also increased by stress in male rats. Progesterone administration to these female and male rats prevented stress-induced prolactin release. To ascertain the part played by dopamine and serotonin in the effect of stress on prolactin release, groups of androgenized and oestrous female rats were treated with bromocriptine or p-chlorophenylalanine methylester hydrochloride (pCPA).(ABSTRACT TRUNCATED AT 250 WORDS)