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Radiofrequency lesions have been placed in the subfornical organ (SFO) or normally cycling and of long-term castrated female rats. The data have shown that, in normal female rats, SFO lesions bring about a disruption of estrous cyclicity in a large number of animals, the majority of which enter a state of prolonged diestrus. In these animals, serum gonadotropin levels are similar to those of regularly cycling animals in the second day of diestrus. In the animals in which estrous cyclicity was still present, an LH surge occurred which was regular in timing and magnitude. On the contrary the proestrous FSH surge was absent, but the usual FSH elevation of the day of estrus was present. SFO lesions were not able to change the high gonadotropin levels typical of the post-castration situation. These results suggest that the SFO may play a role in the control of the "cyclic" but not of the "tonic" release of the two gonadotropins. In particular, it appears from the results that the SFO might be involved in the regulation of the hypersecretion of FSH which occurs during the day of proestrus.

Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.

In order to gain additional information on the role played by the opioids in the control of the secretion of anterior pituitary gonadotropins, morphine (an opioid agonist) and naloxone (an opioid antagonist) have been injected intraventricularly (i.v.t.) into normal or castrated male rats. The animals were killed by decapitation at different time intervals after treatment and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured by radioimmunoassay. Animals injected i.v.t. with 0.9% saline solution and sacrificed at the same time intervals served as controls. When morphine (at the dose of 200 and 400 micrograms/rat) and naloxone (at the dose of 7.5 and 15 micrograms/rat) were injected i.v.t. into normal male rats, a significant increase of serum levels of LH was observed 10 and 20 min after injection. There was no effect at 5, 40 and 60 min. Lower doses of morphine (6.25, 12.5, 25, 50 and 100 micrograms/rat) given i.v.t. were ineffective. When morphine (200 micrograms/rat) and naloxone (either in the dose of 7.5 micrograms/rat or of 15 micrograms/rat) were given simultaneously, serum LH was significantly higher than in the saline-treated controls both at 10 and 20 min. However, the increases of serum LH levels induced by the combined treatment were in both instances lower than those produced by the administration of either drug alone. Morphine (200 micrograms/rat) when administered i.v.t. to normal male rats significantly enhanced prolactin release at 10 and 20 min, and this effect of morphine was blunted by the concomitant i.v.t. administration of naloxone (7.5 and 15 micrograms/rat).(ABSTRACT TRUNCATED AT 250 WORDS)

The intraperitoneal (i.p.) administration of sodium pentobarbital (30 mg/kg) to long-term ovariectomized adult rats results in a prolonged depression of serum LH levels and in a biphasic decrease of serum prolactin (Prl) titers, but does not modify serum levels of FSH. Consequently, caution should be used when interpretating neuroendocrine results obtained in animals submitted to pentobarbital anesthesia.

Adult female rats castrated 4 weeks before were implanted bilaterially into the basomedial area of the amygdala with drugs known to mimic or to counteract the actions of acetylcholine. The animals were sacrificed at different time intervals after the implantation of the different compounds, and serum levels of LH and FSH were measured by radioimmunoassay. The data obtained indicate that the intra-amygdalar implantation of the muscarinic blocker atropine induces a significant increase of the release of LH without altering FSH secretion. The implantation of two cholinomimetic drugs, pilocarpine, an almost pure muscarinic agonist, and carbachol, which possesses both muscarinic and nicotinic properties, exerted an inhibitory effect only on LH release. On the contrary, the intra-amygdala placement of the nicotinic blocker mecamylamine was followed by an increase of FSH with no changes in LH. These observations may suggest that cholinergic signals reaching the amydgala may be of some relevance in the mechanisms controlling gonadotrophine secretion. Muscarinic receptors seem to play an inhibitory role in the regulation of LH secretion, while nicotinic receptors seem to modulate in an inhibitory way FSH release.

The organum vasculosum laminae terminalis (OVLT) was destroyed by radiofrequency lesions in regularly cycling and in long-term ovariectomized adult rats. After OVLT lesion practically all cyclic females (16 out of 22) became dioestrous, as indicated by vaginal smears. At the time of killing these animals (8 days after the lesion) serum LH levels were undetectable, while serum FSH was as low as in cyclic animals in dioestrus. In the few OVLT-lesioned animals which exhibited some sort of oestrous cyclicity, serum LH showed a small subphysiological increase at pro-oestrus; this was not accompanied by a parallel increase in serum FSH and in these animals a delayed peak of FSH occurred on the day of oestrus. Ovariectomized rats bearing OVLT lesions had serum titres of Lh and FSH as high as those of ovariectomized control rats. It is suggested that the OVLT may play a role in the control of the cyclic release of gonadotrophins but is not involved in the tonic regulation of gonadotrophin secretion.

The effects of the compound (+)-1,4-diphenylbutane-2,3-diol (DPB, synthetized in the testes) on gonadotropin secretion have been studied in castrated male rats. DPB, when injected subcutaneously, does not modify serum levels of LH and FSH. On the contrary, the local implantation of DPB in the median eminence of the hypothalamus results in a significant elevation of serum FSH. It is suggested that DPB may play a physiological role in the control of FSH release.

It is known that the neural mechanisms which control PRL and gonadotropin secretion are different in male and female rats. The present experiments have been designed in order to analyze: 1) whether sexual differences exist in the responses of PRL and LH to the opioid antagonist naloxone; and 2) the mechanisms underlying these possible differences. To this purpose the responses of PRL and LH to the sc injection of either saline (0.5 ml) or naloxone (2.5 mg/kg) have been tested in the following four groups of animals: 1) normal male rats; 2) normal female rats; 3) female rats treated on the second day of life with 1.25 mg testosterone (androgenized female rats); and 4) male rats orchidectomized 2 days postnatally (demasculinized male rats). The naloxone challenge has been provided when the animals were 16, 26, and 60 days old; the animals were killed in the afternoon 20 min after treatment. The results obtained have shown that the acute injection of naloxone significantly decreases serum levels of PRL in normal males and in androgenized females at all ages considered. On the contrary, the opioid antagonist was always ineffective in normal females and in neonatally castrated males. The treatment of male rats with naloxone was without any effect on LH release before puberty (at 16 and 26 days of age), but induced a significant increase of serum LH titers after sexual maturation (60 days). In normal females, naloxone brought about a significant increase of serum LH only at 16 and 60 days (animals in estrus), but not at 26 days. Treatment with naloxone did not exert any significant effect on LH release in androgenized females and in deandrogenized males of any age. The present data suggest that, in the rat a sexual difference exists in the opiatergic control of PRL secretion; apparently, the central opioid systems which regulate PRL secretion develop towards a male pattern because of the presence of androgens in the neonatal period. On the contrary neonatal androgens do not seem to exert any important effect in directing the organization of the opiatergic mechanisms controlling LH release.

It is becoming increasingly clear that the effects exerted by opioid agonists and antagonists on the release of gonadotropins and of PRL may vary according to the endocrine milieu. To investigate this issue further, female rats with a regular 4-day estrous cycle have been injected sc with the opioid antagonist naloxone at different hours of the day, during each of the various days of the estrous cycle. The animals were killed 20 min after the sc administration of naloxone (2.5 mg/kg dissolved in 0.9% saline solution) at 1000 and 1600 h on the first and second day of diestrus and at 1000, 1200, 1400, 1600, 1800, and 2000 h on proestrus and estrus. Animals were killed by decapitation, and trunk blood was collected and assayed for LH, FSH, and PRL. The data obtained from naloxone-treated animals were compared to those derived from controls injected sc with 0.9% saline solution and killed at the same time intervals. The sc injections of naloxone stimulated LH release in every phase of the estrous cycle; however the magnitude of the responses was highly variable. Increases of the order of 700-1.000% were observed during the 2 days of diestrus, at 1000 and 1400 h of the day of proestrus, and at 1600, 1800, and 2000 h of the day of estrus. Much higher responses (of the order of 2.700-3.300%) were observed at 1600 h of the day of proestrus and at 1000, 1200, and 1400 h of the day of estrus. The LH response to naloxone appeared to be obliterated at 1800 and 2000 h of the day of proestrus. Serum levels of FSH and PRL were not affected by the treatment at any of the time intervals considered. These findings suggest that, in normally cycling adult female rats, naloxone exerts a stimulatory effect on LH release during each day of the estrous cycle; that the stimulatory effect of naloxone is minimal at the time of the spontaneous proestrous LH surge; and that the effect of naloxone on LH release is, on the contrary, maximal just before the spontaneous proestrous LH surge and up to 1400 h of the day of estrus. The observation that naloxone does not affect FSH and PRL release underlines once more that the central mechanisms controlling LH, FSH, and PRL secretion are different.

The placement of melatonin and of 5-hydroxytryptophol in the median eminence of castrated male rats is followed 5 days later by a significant decrease in pituitary stores of luteinizing hormone. Pituitary reserve of this hormone is also depleted after the implantation of melatonin, 5-hydroxytryptophol, and 5-methoxytryptophol in the reticular formation of the midbrain. It is suggested that these indole compounds, which are normally synthesized in the pineal gland, may intervene in the control of the secretion of luteinizing hormone, possibly by acting on specific receptors localized in the median eminence and in the midbrain.