Rosa Damascena oil improved methadone-related sexual dysfunction in females with opioid use disorder under methadone maintenance therapy - results from a double-blind, randomized, and placebo-controlled trial.

BACKGROUND: Methadone maintenance therapy (MMT) is provided to patients with opioid use disorder (OUD). However, as with all opioids, methadone impacts negatively on sexual function. To counter this, Rosa Damascena oil (RDO) has been used successfully for opioid-dependent male patients under MMT and with methadone-related sexual dysfunction (MRSD). In the present study, we tested the possible influence of RDO on sexual function and sex hormones of opioid-dependent female patients undergoing MMT and with MRSD. METHODS: Fifty female patients (mean age: 38.8 years) diagnosed with OUD, undergoing MMT and with MRSD were randomly assigned either to the RDO or the placebo condition. At baseline, patients completed questionnaires covering socio-demographic and OUD-related information. At baseline, and four and eight weeks later they additionally completed questionnaires on sexual function and happiness. Blood samples to assess thyroid hormones, prolactin, progesterone, and estradiol levels were taken at baseline and eight weeks later (end of the study). RESULTS: Over time sexual function and happiness increased, but more so in the RDO condition than in the placebo condition. Over time, prolactin decreased, and progesterone, and estradiol increased, but again more so in the RDO condition. Sex hormone levels and sexual function were statistically unrelated. CONCLUSIONS: Results from this double-blind, randomized, and placebo-controlled clinical trial showed that opioid-dependent females undergoing MMT and with MRDS did benefit from RDO administration, as sexual function and happiness increased, and female sexual hormone levels changed in positive directions.

Morphometric and hormonal study of the effect of utrica diocia extract on mammary glands in rats / Estudio morfométrico y hormonal del efecto de extracto de utrica diocia en glándulas mamarias en ratas

Urtica diocia is a multipurpose herb in traditional medicine. Its hydroalcoholic extract (20, 50 and 100 mg/kg) administered interaperitoneally to Wistar female rats for 21 consequent days resulted in significant increase in the number of alveoli of mammary glands in doses of 20 and 50 mg/kg. Changes in serum prolactin and alveolar diameter were not significant in comparison with control group. Also, there was an increase in serum prolactin and alveolar diameter in doses of 20 and 50 mg/kg. Utrica diocia extract has positive effects on mammary glands.

Urtica diocia es una hierba de usos múltiples en la medicina tradicional. Su extracto hidroalcohólico (20, 50 y 100 mg/kg) administrado por vía intraperitoneal en ratas hembras Wistar de 21 días resultaron en un aumento significativo en el número de alvéolos de las glándulas mamarias en dosis de 20 y 50 mg/kg. Los cambios en la prolactina sérica y el diámetro alveolar no fueron significativos en comparación con el grupo control. Además, hubo un aumento en la prolactina sérica y en el diámetro alveolar en dosis de 20 y 50 mg/kg. El extracto de Urtica diocia tiene efectos positivos sobre las glándulas mamarias.

Short-term effects of high-dose khat on sperm parameters and reproductive hormonal levels in olive baboons (Papio anubis).

The biological effects of khat (Catha edulis) on reproduction and fertility are inadequately investigated and controversial, hence we determined the effects of oral administration of high-dose khat on sperm parameters and male hormonal levels in olive baboons. In this study, 6 male baboons received a high dose of khat (500 g/week) during 1 month. Electroejaculation for sperm studies (concentration, motility and chromatin integrity) and plasma collection for hormonal analysis (testosterone, prolactin and cortisol) were done weekly during 1 month before and 1 month during khat administration as well as 2 weeks after the last dose of khat administration. Administration of khat extract induced a significant reduction in sperm motility (p = 0.008), sperm count (p = 0.041), sperm chromatin integrity (p = 0.0003), testosterone levels (p = 0.035) and prolactin levels (p = 0.0115), but not in cortisol levels and sperm volume (p > 0.05). The results suggest that high-dose khat decreases sperm quality and testosterone and hence may contribute to male infertility.

The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study.

OBJECTIVE: It has been shown that coenzyme Q(10) (CoQ(10)) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ(10) supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT. PATIENTS AND METHODS: Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ(10) 300 mg orally twice daily for 12 months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12 months after CoQ(10) discontinuation. RESULTS: Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ(10) therapy by 113.7, 104.8, and 78.9%, respectively (all Ps < 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4 ± 4.7 months. CONCLUSIONS: CoQ(10) supplementation improves semen quality with beneficial effect on pregnancy rate.

Some effects of risperidone and quetiapine on growth parameters and hormone levels in young pigtail macaques.

OBJECTIVE: Atypical antipsychotic drugs are prescribed to young children for a number of symptoms, some with no Food and Drug Administration approval for children. Effects on growth of children have received little experimental study. We assessed the effects of two atypicals, risperidone and quetiapine, on growth, prolactin, and thyroid hormones of young pigtail macaques (macaca nemestrina), modeling potential effects on 4-8-year-old children. METHODS: Subjects were studied blindly after random assignment to risperidone (N = 10), quetiapine (N = 10), or placebo (N = 20). Four phases were studied: (1) predrug, 9-12 months of age; (2) low dose (risperidone 0.025 mg/kg, quetiapine 2 mg/kg), 13-16 months; (3) high dose (risperidone 0.05 mg/kg, quetiapine 4 mg/kg), 17-20 months; (4) postdrug, 21-24 months. Body weight was measured daily, skeletal dimension monthly, and bone mineralization and hormones bimonthly. RESULTS: Our primary result showed that, compared with placebo, neither drug had detrimental effects on body weight, skeletal dimensions, or thyroid hormones. However, in a transient effect, bone density was lower following low-dose risperidone than either quetiapine or placebo. In both drug phases, risperidone prolactin was higher than the other groups, which did not differ. The higher prolactin of the risperidone group may partially explain the bone density effect. CONCLUSION: This 16-month study of young, developing pigtail macaques given risperidone at doses from 0.025 to 0.05 mg/kg or quetiapine at doses from 2 to 4 mg/kg suggests that these drugs are safe for normal body weight and skeletal growth in young pigtail macaques given an adequate diet, although these drugs are known to cause significant weight gain and other metabolic changes in some children, adolescents, and adult humans. In addition, the results, although transient in our study, also suggest that research in children on bone mineralization effects of risperidone, and possibly other antipsychotic drugs, may be warranted.

Effect of Sauropus androgynus leaf extracts on the expression of prolactin and oxytocin genes in lactating BALB/C mice.

Sauropus androgynus is traditionally consumed by Indonesians and is believed to increase breast milk production during lactation. Lactation, a process of milk synthesis and secretion, occurs with the help of 2 hormones, prolactin and oxytocin. The expressions of genes encoding prolactin and oxytocin were analyzed in lactating BALB/C mice brains using qRT-PCR. A total of 24 lactating BALB/C mice were fed with experimental diets for 12 days. Two groups of lactating mice were fed with diets containing either young or mature S. androgynus leaf extracts. For the control, one group of lactating mice was fed a diet without S. androgynus leaf extracts. Supplementation of young S. androgynus leaf extracts increased the expression of prolactin and oxytocin genes in lactating mice 9.04- and 2.25-fold, respectively. Meanwhile, supplementation of mature S. androgynus leaf extracts increased the expressions of both genes 15.75- and 25.77-fold, respectively, compared to the control group. The result suggested that mature S. androgynus leaf extracts significantly increased the expressions of both genes in lactating BALB/C mice and was predicted to correlate with papaverine content, which is only detected in mature S. androgynus leaves at a concentration of 0.38 ± 0.04 µg·ml(-1).

Effects of dietary equol administration on the mammary gland in ovariectomized Sprague-Dawley rats.

OBJECTIVE: To evaluate the effects of dietary equol, a metabolite of soy-derived daidzein or formononetin present in red clover, on the mammary gland of ovariectomized Sprague-Dawley rats. DESIGN: Sixty ovariectomized rats were divided into five groups (n = 12) and fed soy-free chow with the addition of equol (50 mg/kg chow and 400 mg/kg chow) or estradiol-3 benzoate (E2B) (4.3 mg/kg chow and 17.3 mg/kg chow). The control group received soy-free chow only. After 3 months animals were killed, blood was collected, and the mammary glands were removed for histological and immunohistochemical evaluation. RESULTS: Equol and E2B treatment significantly increased serum equol and 17beta-estradiol concentrations, respectively. Serum prolactin in animals treated with high-dose equol was also significantly higher than in the controls. Animals treated with high-dose equol had a significantly higher number of terminal ducts and type II lobules compared with controls. This was also apparent in animals treated with low- and high-dose E2B, but a higher number of type I lobules also was seen. Compared with controls, animals treated with high-dose equol had a significantly higher percentage of proliferating cell nuclear antigen-positive cells in terminal ducts and type II lobules. The percentage of progesterone receptor-positive cells in animals treated with high-dose equol was significantly higher only in type II lobules. In animals treated with low- and high-dose E2B, the percentage of proliferating cell nuclear antigen- and progesterone receptor-positive cells was significantly higher in all the mammary structures. Low-dose equol did not have any effects on the parameters listed above. CONCLUSIONS: High-dose dietary equol administration to ovariectomized rats exerts clear mammotropic effects.

Ginkgo biloba extract enhances male copulatory behavior and reduces serum prolactin levels in rats.

The aim of this study was to investigate the effects of Ginkgo biloba extract (EGb 761) on male copulatory behavior in rats. EGb 761 (1 mg/ml) induced significant production of testosterone (T) in rat Leydig cells in vitro. Its effects on sexual behavior were then tested in Long-Evans male rats after 7, 14, 21, or 28 days of oral gavage of vehicle (distilled water) or EGb 761 at doses of 10, 50, or 100 mg/kg. Administration of 50 mg/kg of EGb 761 for 28 days and of 100 mg/kg for 14 or 21 days significantly increased intromission frequency compared to controls on the same day. An increase in ejaculation frequency was seen after treatment with 50 mg/kg of EGb 761 for 14, 21, or 28 days when compared to either the control group on the same day or the same group on day 0. A reduction in ejaculation latency was only seen after administration of 50 mg/kg of EGb 761 for 14 days compared to the vehicle-treated group. After treatment for 28 days, no significant difference was seen in mount latency, intromission latency, serum T levels, reproductive organ weight, sperm number, or levels of the metabolite of dopamine, 3,4-dihydroxyphenylacetic acid in the brain with any dose of EGb 761, but significantly reduced serum prolactin levels and increased dopamine levels in the medial preoptic area and arcuate nucleus were seen at the dose of 50 mg/kg. These findings show that EGb 761 (especially at the dose of 50 mg/kg) enhances the copulatory behavior of male rats and suggest that the dopaminergic system, which regulates prolactin secretion, may be involved in the facilitatory effect of EGb 761.

Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a traditional herbal medicine, stimulates lactation with increase in secretion of prolactin but not oxytocin in the postpartum period.

The aim of the present investigation was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin, a traditional Japanese herbal medicine, in stimulating lactation in the postpartum period. We enrolled 82 women who had a normal delivery in Osaka Medical College Hospital, and randomly assigned them to the following two groups: a group of 41 women who received Xiong-gui-tiao-xue-yin at a dose of 6.0 g/day (Group X), and a group of 41 women who received ergometrine (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). Volume of lactation was determined daily until Day 6 postpartum. Plasma prolactin and oxytocin concentration were measured at Days 1 and 6 postpartum. The results showed that volume of lactation was significantly higher in Group X than in Group E at Days 4 (p = 0.042), 5 (p = 0.038), and 6 (p = 0.046). Significant differences between Groups X and E were noted in plasma prolactin concentration at Days 1 (157.9 +/- 78.2 ng/ml and 129.1 +/- 64.8 ng/ml; p = 0.037) and 6 (167.5 +/- 95.4 ng/ml and 117.1 +/- 53.6 ng/ml; p = 0.0042) postpartum. On the other hand, at Day 1, oxytocin concentration was significantly higher in Group E than in Group X (p = 0.0024). No adverse effects were observed in this study. The results of our study demonstrate the beneficial effects of Xiong-gui-tiao-xue-yin on lactation, with increase in prolactin level without increase in oxytocin level in the postpartum period. Therefore, Xiong-gui-tiao-xue-yin can be expected to improve lactation in women in the postpartum period. Further detailed bio-pharmacological studies and clinical trials to investigate the properties of this drug are warranted.

Antifertility activity of the methanolic leaf extract of Cissampelos pareira in female albino mice.

meenakshi Cissampelos pareira Linn. is one of the folk medicinal plants commonly used as antifertility agent in some places of India. The aim of the present study was to evaluate the validity of the antifertility effect of the leaf extract. Cissampelos pareira leaf extract, when administered orally, altered the estrous cycle pattern in female mice, prolonged the length of estrous cycle with significant increase in the duration of diestrus stage and reduced significantly the number of litters in albino mice. The analysis of the principal hormones involved in estrous cycle regulation showed that the plant extract altered gonadotropin release (LH, FSH and prolactin) and estradiol secretion. The results indicated the antifertility effect of Cissampelos pareira leaf extract in female albino mice. The oral LD50 of the extract was found to be 7.3 g/kg in mice.

Effect on prolactin secretion of Echinacea purpurea, hypericum perforatum and Eleutherococcus senticosus.

It has been recently reported that prolactin (PRL) plays an important role in immune system regulation. In this study we investigated the activity of three natural drugs with immunomodulatory activity: Echinacea purpurea (EP), Hypericum perforatum (HP) and Eleutherococcus senticosus (ES) on PRL production. Male rats were orally treated with two different doses (30 and 100 mg/kg) of extract of these drugs for 3 or 15 days. A 3-day treatment was not able to modify PRL serum levels, whereas a 15-day treatment with EP and HP at the higher dose significantly inhibits PRL production. A treatment with ES was always ineffective. A possible mechanism for this effect could be that both HP and EP extracts display a direct dopaminergic activity, although an involvement of the GABA-ergic system cannot be excluded.

Alpha-melanocyte-stimulating hormone through melanocortin-4 receptor inhibits nitric oxide synthase and cyclooxygenase expression in the hypothalamus of male rats.

There is evidence that alpha-melanocyte-stimulating hormone (alpha-MSH) has immunomodulatory and anti-inflammatory actions within the brain. In this study, we tested whether these actions are due to inhibition of the synthesis of nitric oxide (NO) and prostaglandins induced by lipopolysaccharide (LPS). Since melanocortin subtype MC4 receptor has been detected in the hypothalamus, we investigated the effect of central administration of alpha-MSH and HS024 (a selective MC4 receptor antagonist) on the gene expression of inducible, neuronal and endothelial NO synthase (iNOS, nNOS and eNOS) and on cyclooxygenase (COX-1 and COX-2) expression in the mediobasal hypothalamus (MBH) of LPS-treated male Wistar rats. Peripheral administration of LPS (250 microg/rat, 3 h) induced iNOS and COX-2 gene expression in the MBH. This stimulatory effect was reduced by alpha-MSH (3 nmol/rat) injected 30 min before LPS. alpha-MSH and HS024 (1 nmol/rat) alone had no effect on iNOS and COX-2 expression. The action of alpha-MSH on LPS-induced iNOS and COX-2 mRNA levels was not observed in the presence of HS024, suggesting that MC4-R may be involved in the modulatory effect of alpha-MSH. None of these treatments produced any modifications in nNOS, eNOS and COX-1 expression in MBH. The increase in serum corticosterone levels induced by LPS was attenuated by alpha-MSH. Both LPS and alpha-MSH decreased serum LH and prolactin levels. HS024 failed to modify the inhibitory effects of LPS and alpha-MSH on prolactin release but reverted the effect of LPS on LH secretion, indicating that MC4-R activation may be involved in the effects of alpha-MSH on LH secretion in male rats. When we examined the in vitro effect of LPS (10 microg/ml) and LPS plus interferon-gamma (IFN-gamma, 100 ng/ml) on iNOS expression in MBH, an increase in iNOS mRNA levels was observed only in the presence of LPS + IFN-gamma. This stimulatory effect was attenuated in the presence of alpha-MSH (5 microM), which by itself had no effect. No changes were found in nNOS, eNOS, COX-1 or COX-2 expression. These results indicate that alpha-MSH reduces the induction of iNOS and COX-2 gene expression at the hypothalamic level during endotoxemia and suggest that endogenous alpha-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus.

Genistein, a phytoestrogen, effectively modulates luteinizing hormone and prolactin secretion in ovariectomized ewes during seasonal anestrus.

Through binding with estrogen receptors, phytoestrogens, plant-derived estrogen-like compounds, affect numerous reproductive functions. It is not known whether these compounds are capable of evoking effective changes in luteinizing hormone (LH) and prolactin (PRL) secretion in ewes by acting directly within the central nervous system (CNS). The hypothesis studied was that genistein, infused for several hours into the third ventricle, could immediately affect LH and PRL secretion in ovariectomized (OVX) ewes during seasonal anestrus. Two doses of genistein, 1 microg/100 microl/h (total 4 microg, n = 7) and 10 microg/100 microl/h (total 40 microg, n = 7), were infused intracerebroventricularly from 12.00 to 16.00 h and blood samples were collected from 8.00 to 20.00 h at 10-min intervals. Randomly selected ewes were infused with a vehicle (control, n = 5). The mean plasma LH concentration in control ewes was significantly (p < 0.01) higher during infusion of the vehicle than before the infusion. It remained on an insignificantly changed level after the infusion. The frequency of LH pulses in control ewes did not differ significantly before, during, or after vehicle infusion. In ewes infused with a lower dose of genistein, plasma LH concentrations decreased significantly (p < 0.001) after the infusion, as compared with the values noted before and during genistein infusion. Only a tendency towards a decrease in LH pulse frequency occurred after infusion of a lower dose of genistein. In ewes infused with a higher dose of genistein, the plasma LH concentration decreased significantly (p < 0.01) after phytoestrogen administration as compared with the values noted before and during infusion. The frequency of LH pulses was also significantly (p < 0.01) lower after genistein administration. Because the changes in PRL secretion were more dynamic in response to genistein infusion, the statistical analysis included 2-hour periods. The mean plasma PRL concentration in control animals was significantly enhanced (p < 0.01) only during the first 2-hour period of sampling. After that it decreased and remained on an unchanged level up to the end of sampling. Similar changes in PRL secretion were observed in both experimental groups before genistein infusion. In contrast, significant (p < 0.01 to p < 0.001) increases in PRL concentration were noted regularly during and shortly after the genistein infusion in either low-dose or high-dose genistein-infused ewes, compared with the concentrations noted before genistein treatment. Plasma PRL concentrations during and after genistein infusion in both experimental groups were also significantly higher than the control (p < 0.01 to p < 0.001). The presented data demonstrate that genistein, a phytoestrogen, may effectively modulate LH and PRL secretion in OVX ewes by acting within the CNS.

Peripheral selectivity and apparent efficacy of dynorphins: comparison to non-peptidic kappa-opioid agonists in rhesus monkeys.

The potency and effectiveness of dynorphin A(1-17), E-2078 (a synthetic dynorphin A(1-8) analog) and non-peptidic kappa-opioid agonists were studied in rhesus monkeys in two assays: 1) a drug discrimination assay with the centrally-penetrating kappa-agonist U69,593 as the training stimulus (n=3) and 2) a prolactin release assay; a neuroendocrine effect thought to be mediated by kappa-receptors located in hypothalamic nuclei outside the blood-brain barrier. The non-peptidic kappa-agonists, U69,593 and bremazocine (0.00032-0.01 mg/kg, s.c.) were dose-dependently generalized by all the subjects trained to discriminate U69,593. U69,593 and bremazocine also caused dose-dependent prolactin release (n=4). By contrast, dynorphin A(1-17) and E-2078 (0.1-1 mg/kg, i.v.) were only generalized by one of the U69,593 discriminating subjects. However, both these dynorphins produced potent and robust prolactin release (0.0032-0.032 mg/kg, i.v.), when tested under an identical time course design as above. Naltrexone (0.1 or 0.32 mg/kg), caused a parallel rightward shift in the dose-effect curves for all the above ligands, consistent with kappa-receptor mediation of this neuroendocrine effect. The peripherally selective antagonist, quaternary naltrexone (0.32 mg/kg, s.c.) partially blocked the neuroendocrine effects of U69,593 and E-2078 (0.0032 mg/kg, s.c. and i.v., respectively). Overall, these findings are consistent with the hypothesis that the dynorphins act as high efficacy, peripherally selective kappa-agonists following systemic administration in primates.

Effect of seizures and antiepileptic drugs on prolactin secretions.

OBJECTIVE: To study the effect of seizures and antiepileptic drugs on prolactin (PRL) secretions. METHODS: Serum PRL level was measured by radioimmunoassay in 110 epileptic patients who received different treatment protocols with antiepileptic drugs (AEDs), and the test was also performed in 64 of these patients before and after seizures. Another 21 untreated epileptic patients and 42 healthy subjects served as the control groups. RESULTS: Serum PRL level was significantly increased after seizures, which peaked at 15 min postictal and attained the levels more than 5-fold the baseline in 59 patients. At 90-minute postictal, PRL levels decreased in 57 patients and dropped within normal range in 38 patients. The changes of hormone levels correlated significantly with the types of seizures. The basal PRL levels in patients with exclusive phenytion (PHT) or valproate (VPA), and in those with combined ministration of carbamazpine (CBZ+VPA+PHT), were significantly lower than the control levels (P<0.05). Patients receiving treatment with traditional Chinese medicine had comparable serum PRL levels with the normal control group (P>0.05). CONCLUSION: Seizures of epilepsy and medication with AEDs given as either monotherapy or polytherapy affect the secretion of PRL in the pituitary, but traditional Chinese medicine therapies does not.

Lipopolysaccharide- and tumor necrosis factor-alpha-induced changes in prolactin secretion and dopaminergic activity in the hypothalamic-pituitary axis.

Bacterial lipopolysaccharide (LPS) affects pituitary hormone secretion, including prolactin release, by inducing synthesis and release of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Since prolactin is mainly under tonic inhibitory control of dopamine, we investigated the effect of LPS and TNF-alpha on the hypothalamic-pituitary dopaminergic system. LPS (100-250 microg/rat, i.p.) decreased serum prolactin levels after 1 or 3 h. Sulpiride, a dopaminergic antagonist, increased serum prolactin and blocked the inhibitory effect of LPS. LPS increased hypothalamic dopamine and DOPAC concentrations and the DOPAC/dopamine ratio both in mediobasal hypothalamus and the posterior pituitary. LPS also enhanced dopamine and DOPAC concentration in the anterior pituitary. LPS elevated plasma levels of epinephrine, norepinephrine and dopamine but it did not modify the concentration of epinephrine or norepinephrine in the tissues studied. The administration of TNF-alpha (i.c.v., 1 h, 100 ng/rat) decreased serum prolactin but did not affect plasma catecholamine levels. TNF-alpha did not modify the DOPAC/dopamine ratio in hypothalamus or posterior pituitary but increased dopamine and DOPAC concentrations in the anterior pituitary. Incubations of hypothalamic explants showed that TNF-alpha did not modify in vitro basal dopamine release and reduced K(+)-evoked dopamine release. On the contrary, incubations of posterior pituitaries showed that TNF-alpha significantly increased basal and K(+)-evoked dopamine release. These results indicate that LPS and TNF-alpha increase dopamine turnover in the hypothalamic-pituitary axis. This increase in dopaminergic activity could mediate the inhibitory effect of LPS and TNF-alpha on prolactin release. Furthermore, the increase in dopaminergic activity elicited by LPS could be mediated by an increase in hypothalamic TNF-alpha during endotoxemia.

The improvement of luteal insufficiency in fecund women by tokishakuyakusan treatment.

The effect of tokishakuyakusan, a Chinese herbal medicine, was examined, in vivo, in women with luteal insufficiency and in women with normal menstrual cycles. Luteal insufficiency was determined by daily measurement of basal body temperature and plasma progesterone levels. Tokishakuyakusan improved luteal insufficiency. Furthermore, the effects of tokishakuyakusan on prolactin, gonadotropins, steroids, angiotensin II, ANP and renin levels in the blood of women with normal menstrual cycles were studied, as were the medicine's effects on estrogens, pregnenediol and LH in the urine of the same women. Tokishakuyakusan had no adverse effect on hormonal levels in either blood or urine. Furthermore, no clinical side effects were detected. These results suggest that tokishakuyakusan improves luteal insufficiency in women but does not affect the hormonal levels of women with normal menstrual cycles.

Effects of prolactin-releasing peptide on tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in estrogen-treated female rats.

Both systemic and central effects of a newly discovered prolactin (PRL)-releasing factor (PRF), prolactin-releasing peptide (PrRP), were determined in this study. Systemic injection of PrRP (1 and 10 microg/rat, i.v.) stimulated PRL secretion in ovariectomized, estrogen-treated rats similar to the effect of another PRF, thyrotropin-releasing hormone (TRH). Pretreatment with a dopamine D2 receptor antagonist, sulpiride (1 microg/rat, i.v.), potentiated the stimulatory effect of both PrRP and TRH on PRL secretion. Using the double-labeling immunohistochemical method, PrRP-immunoreactive terminals were found in close contact with tyrosine-hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus. Central administration of PrRP (0.1-1,000 ng/rat, i.c.v.) stimulated tuberoinfundibular but not nigrostriatal dopaminergic neuronal activity in 15 min. Levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence and striatum were used as indices for tuberoinfundibular dopaminergic (TIDA) and nigrostriatal dopaminergic neuronal activities, respectively. The serum PRL level, however, was not significantly changed. Similar treatment with TRH (10 ng/rat, i.c.v.) stimulated and inhibited TIDA neuronal activity and serum PRL, respectively, at 30 min. In summary, PrRP may play a role in both the central and peripheral control of PRL secretion.