Study on the neuroendocrinological control of prolactin release in early puerperium

The purpose of this study is to investigate the neuroendocrinological control mechanism of prolactin (PRL) acting on the hypothalamo-pituitary axis during early puerperium. The puerperal women consisted of three groups: the breast-feeding group (n = 39), the bromocriptine (BRC)-treated group (5 mg/day, n = 17) and naloxone-treated group (1 mg iv, n = 16). In each group, 10 mg metoclopramide (MCP), 500 micrograms TRH or 400 mg cimetidine was given intravenously. 1) The plasma PRL levels increased significantly after the injection of MCP, TRH and cimetidine. The peak values of delta PRL levels were 447.0 +/- 62.3 ng/ml after MCP, 278.3 +/- 65.1 ng/ml after TRH and 86.5 +/- 27.3 ng/ml after cimetidine. 2) This PRL increase after the injection of MCP and cimetidine was suppressed significantly by pretreatment with BRC. However, the PRL increase after TRH was not suppressed by pretreatment with BRC. 3) Naloxone had no significant effect on PRL response to MCP and TRH, since the plasma PRL levels rose significantly after the injection of MCP and TRH in the naloxone-treated group. These results revealed that there were different mechanisms of PRL release in MCP and TRH. Furthermore, the PRL releasing mechanism was influenced by histamine H2-receptor, but was not influenced by opioid peptide in early puerperium.     

Exaggerated prolactin response to thyrotropin-releasing hormone and metoclopramide in primary testicular failure

Twenty-eight severely oligospermic and azoospermic men aged 20 to 42 years were challenged with luteinizing hormone (LH)-releasing hormone (LHRH), thyrotrophin-releasing hormone (TRH), and the dopaminergic antagonist, metoclopramide, given at 30-minute intervals. According to basal gonadotropin levels, the patients were subdivided into three groups: those with severe testicular failure (basal LH > 20 mIU/ml and FSH > 14 mIU/ml); those with moderate testicular failure with predominant seminiferous tubule involvement (LH < 20 mIU/ml and FSH > 14 mIU/ml) and those with mild testicular failure (LH < 20 mIU/ml and FSH < 14 mIU/ml. With one exception, mean basal prolactin (PRL) levels were normal in all patients. In all three groups, however, there was an exaggerated PRL response to TRH, the response in severe and moderate testicular failure being greater than that in mild testicular failure. The response to metoclopramide was increased only in the first two groups, not in the group with mild testicular failure. When individual patients and control subjects were considered together, the peak PRL response to TRH correlated with both basal and peak gonadotropin responses to LHRH. However, the PRL responses did not correlate with 17 beta-estradiol, estrone, testosterone, or the estradiol-testosterone ratio. It is concluded that oligospermic and azoospermic subjects with the most severe testicular failure and the highest gonadotropin levels have the greatest PRL increases after TRH and metoclopramide, indicating that the PRL response is related to the degree of testicular failure.     

Prolactin and its response to the luteinizing hormone-releasing hormone thyrotropin-releasing hormone test in patients with endometriosis before, during, and after treatment with danazol

Basal levels of prolactin (PRL) were studied in 16 normal women and in 60 women with endometriosis, 37 of whom were infertile. In addition, the authors studied the response to an intravenous (IV) injection of luteinizing hormone-releasing hormone (LH-RH) (100 micrograms) plus thyrotropin-releasing hormone (TRH) (300 micrograms) in the 16 normal women and in 18 endometriosis patients, examining the basal PRL and thyrotropin, and at 15, 30, 45, 60, and 120 minutes after the IV bolus. After laparoscopy and/or conservative surgery, the patients were treated with danazol for 6 months and a second laparoscopy was performed. The LH-RH/TRH test was carried out in the third month of danazol treatment in 6 endometriosis patients and before the second laparoscopy in 11 patients. The results show that there was both an increase in the mean basal levels of PRL and in the percentage of cases of moderate hyperprolactinemia in endometriosis patients. There also was a greater rise in PRL with the LH-RH/TRH test in moderate and severe endometriosis. The PRL response was significantly greater in endometriosis than in normal women, and was not related to TSH response. Danazol treatment reduced significantly the PRL response. The PRL response before treatment was significantly higher in patients who after treatment showed persistent endometriosis at the second laparoscopy. This could suggest a lower effectiveness of danazol in patients with endometriosis and a PRL hyper-response to LH-RH/TRH.     

Serum prolactin levels during sleep and in metoclopramide stimulation in normoprolactinemic anovulation and ovulation induction with bromocriptine

Diurnal and nocturnal serum prolactin (PRL) levels were determined in 37 normoprolactinemic anovulatory (nPRL-Anov) patients and 6 normal cycling women each in the early follicular phase (EFP) and the luteal phase (LP). PRL responsiveness to metoclopramide (MCP) was assessed. The nPRL-Anov patients received 5mg/day bromocriptine (CB-154) for 2 months and ovulation was investigated. To the CB-154 non-responders was added 150mg/day clomiphene (CL) for 5 days. The nPRL-Anov patients were classified into 3 groups; i.e. I: those who ovulated with CB-154 (n = 14), II: those who ovulated with CB-154 + CL (n = 6), and III: those who failed to ovulate (n = 10). Nocturnal serum PRL levels in I (42.0 +/- 26.2ng/ml; M +/- SD) were significantly higher than those in EFP, II and III (p less than 0.05). Eleven (78.6%) of I had nocturnal PRL levels higher than 25ng/ml. The peak PRL values at MCP provocation were significantly higher in I (213.3 +/- 89.1ng/ml) than in EFP, II and III (p less than 0.01). Thirteen (92.9%) of I had peak PRL values more than 150ng/ml. The peak PRL values and nocturnal PRL levels correlated. There were some exhibiting nocturnal or latent hyperprolactinemia, who responded effectively to CB-154, among nPRL-Anov patients. A MCP provocation test could be used in prediction of the efficacy of CB-154 treatment when applied to nPRL-Anov patients.     

Prolactin response to thyrotropin-releasing hormone in women with infertility and/or randomly elevated serum prolactin levels

Infertile women with normal serum prolactin (PRL) levels have been known to establish a pregnancy after the use of bromocriptine, a dopamine agonist. These data imply that there may be a group of women with a slight but significant increase in PRL secretion that may have resulted in their infertility. This study evaluates the thyrotropin-releasing hormone (TRH)-induced PRL and thyroid-stimulating hormone (TSH) response in normal women (NL, n = 6), women with anovulation and/or inphase endometrial biopsies (AN/IN, n = 12), and women with histologic evidence of luteal phase deficiency (LPD, n = 12). Most of these women were found to have elevated serum PRL values on random testing. There was a statistically significant increase in PRL response at all time intervals after TRH between the NL and AN/IN groups compared with the group with LPD on the basis of repeated measures analysis (P = 0.0013). There was no statistical difference in the TSH response between these three groups. Although the PRL response was statistically different, individual PRL response patterns were not diagnostic. It appears from these data that there is an increased PRL secretion in infertile women who have histological evidence of a LPD.     

Prolactin response to thyrotropin-releasing hormone in normal and complicated late pregnancies.

Maternal serum prolactin level (PRL) was determined with radioimmunoassay in normal and complicated late pregnancy. The mean basal PRL levels were not statistically different among normal (179.3 ng/ml), preeclamptic (169.7 ng/ml), hypertensive (171.4 ng/ml), twin (194.8 ng/ml), or diabetic pregnancies (134.4 ng/ml), although 3 of 17 diabetic women had abnormally low PRL levels. The PRL response to 200 micrograms of intravenously administered thyrotropin-releasing hormone (TRH) was investigated and found similar in normal, preeclamptic, hypertensive, and twin pregnancies. There was no response to TRH in 2 of 3 diabetics with a low basal PRL level. One of these diabetic patients experienced an unexplained intrauterine death 4 weeks later; the others delivered term infants, 1 of whom died of respiratory distress syndrome (RDS). These preliminary results suggest that low basal PRL levels and unresponsiveness to TRH may be related to a poor fetal or neonatal prognosis in diabetic pregnancies.     

Hyperprolactinaemic Amenorrhoea in Hong Kong

In a retrospective study of 595 patients attending the Menstrual Disorder Clinic from January, 1978 to December, 1981, 92 patients (15.5%) had raised serum prolactin (PRL) levels (greater than 25 ng/ml) on 2 or more separate occasions with a mean (+/- S.E.M.) value of 67.1 +/- 2.5 ng/ml. Galactorrhoea was found in 27.2% of the hyperprolactinaemic patients. Primary amenorrhoea was observed in 1 patient (1.1%) with serum PRL level of 68 ng/ml. Secondary amenorrhoea of longer than 6 months' duration occurred in 61 patients (66.3%) with mean PRL level 84.2 +/- 3.3 ng/ml. The 30 patients (32.6%) with irregular menstruation had a mean PRL level of 47.2 +/- 3.3 ng/ml. Investigations revealed that 43 patients (46.7%) had idiopathic hyperprolactinaemia, 14 patients (15.4%) had drug induced hyperprolactinaemia and 1 patient (1.1%) had hypothyroidism; 18 patients (19.5%) had suspected pituitary microadenoma and 16 patients (17.2%) had abnormal radiographic findings. Bromocriptine treatment was given to 38 patients, 13 with abnormal tomographic findings (mean serum PRL greater than 100ng/ml); 18 with suspected pituitary microadenoma (mean serum PRL 94 +/- 2.7 ng/ml) and 7 with idiopathic hyperprolactinaemia (mean serum PRL 65 +/- 4.7 ng/ml). All patients (38/38) responded to treatment with restoration of menstruation and cessation of galactorrhoea within 1 to 3 months. Mean PRL level was 21.6 +/- 5.2 ng/ml at the time of response. Thirteen patients subsequently became pregnant and all delivered healthy babies.     

The metoclopramide test: a useful tool with the luteinizing hormone-releasing hormone test in distinguishing between constitutional delay of puberty and hypogonadotropic hypogonadism

To evaluate the effectiveness of intravenous metoclopramide, alone or in combination with luteinizing hormone-releasing hormone (LH-RH), in distinguishing between constitutional delay of puberty and hypogonadotropic hypogonadism, 12 patients with constitutional delay of puberty and 10 patients with hypogonadotropic hypogonadism were studied. All patients received 10 mg/m2 of intravenous metoclopramide and 100 micrograms of intravenous LH-RH on separate days. The mean prolactin (PRL) response following metoclopramide was significantly higher in the constitutional delay of puberty group when compared with the hypogonadotropic hypogonadism patients (P less than 0.01 at 15, 30, 45, and 60 minutes); all patients with constitutional delay of puberty increased their PRL level to greater than or equal to 60 ng/ml, except one who had a peak PRL level of 38 ng/ml. While only 2 of the hypogonadotropic hypogonadism subjects reached a peak PRL concentration of greater than or equal to 60 ng/ml, 4 had peak PRL levels greater than 38 ng/ml. The mean LH and follicle-stimulating hormone (FSH) responses after LH-RH were significantly higher in the constitutional delay of puberty group (P less than 0.01 at 30, 45, and 60 minutes for LH and P less than 0.01 at 45 and 60 minutes for FSH). All constitutional delay of puberty subjects responded to both the metoclopramide and LH-RH tests, while patients with hypogonadotropic hypogonadism responded only to one or to neither of these tests. Therefore, while metoclopramide alone did not allow us to clearly distinguish constitutional delay of puberty from hypogonadotropic hypogonadism, the combined use of both of these stimuli permitted us to detect all subjects with constitutional delay of puberty.     

Long-term effects of time, medical treatment and pregnancy in 176 hyperprolactinemic women.

The changes in plasma prolactin (PRL) concentrations were studied in 176 hyperprolactinemic women over periods of 6-180 months, to evaluate the independent effects of time, drugs and pregnancy on the evolution of prolactinemia. CT scans showed pituitary adenoma in 87 (9 macroadenoma), the clinical presentations for 110 patients there amenorrhea, for 37 abnormal cycles and 29 had anovulatory sterility as an isolated symptom. 107 women underwent 191 cycles of dopaminergic treatment and 73 had pregnancies (86), either spontaneously or as a consequence of the treatment. Changes in prolactin induced by medical treatment and pregnancy were recorded and the spontaneous changes in prolactin in 38 patients (17 with adenoma) were followed over periods of 6-72 months. Final mean PRL concentrations were lower than basal though not significantly, in both 'functional' (54.4 vs. 79.2 ng/ml) and prolactinoma patients (87.3 vs. 116.4 ng/ml). Separate calculation of changes in prolactin after the course of medical treatment, pregnancies or 'just waiting' periods showed mean PRL concentrations to be significantly lower only for 'functional' patients after pregnancy. On the other hand, PRL variations in individual patients revealed that: (1) spontaneously, PRL rarely becomes lower over a few years; (2) dopaminergic treatment was associated with normalization of PRL in 13% of women; and (3) pregnancy normalized prolactin concentrations in 29% of the patients. Chi-square analysis of the PRL-lowering frequencies in functional patients showed a high cure rate for pregnancy (P less than 0.0001) and a lesser but still significant effect of drugs (P less than 0.025).     

Differential prolactin response to oral metoclopramide in nulliparous versus parous women throughout the menstrual cycle

OBJECTIVE: To analyze if serum prolactin (PRL) changed throughout the menstrual cycle and if parous women have lower PRL than nulliparous women. DESIGN: A prospective study of PRL was performed in basal conditions and during oral metoclopramide stimulation on days 7, 14, and 21 of menstrual cycle. SETTING: Instituto Nacional de Perinatología, third level medical institution. PATIENTS: Four parous (group A) and seven nulliparous (group B) healthy volunteer women entered and finished the study. INTERVENTIONS: Women were studied each day before and every 30 minutes during 2 hours after oral metoclopramide (10 mg). MAIN OUTCOME MEASURE: Duplicate PRL determinations were performed by radioimmunoanalysis. Hypothesis was formulated before data collection. RESULTS: Group A and B had similar basal PRL levels and no within group differences existed in response to metoclopramide, regardless of the day studied. Group A had lower PRL increments than group B from 60 to 120 minutes on days 14 and 21 (P less than 0.05); the peak increments also were lower on days 7, 14, and 21 (P less than 0.05). CONCLUSIONS: Parous women had a diminished PRL response. Although the dopaminergic tone was similar throughout the menstrual cycle within each group, two distinct levels of dopaminergic tone existed in parous and nulliparous women.     

Prolactin synthesis and release during pregnancy and puerperium

Prolactin (PRL) synthesis and its release following thyrotropin-releasing hormone (TRH) administration during pregnancy and puerperium was studied in 45 women. Mean baseline E2 increased from 1,900 +/- 384 (SEM) pg/ml in the first trimester to 3,520 +/- 849 in the second trimester (P less than 0.05) and 43,057 +/- 5,765 pg/ml in the third trimester (P less than 0.001) of pregnancy. Mean baseline progesterone increased from 27.6 +/- 3.2 ng/ml in the first trimester to 41.9 +/- 6.6 in the second trimester (P less than 0.01) and 109.3 +/- 11.2 ng/ml in the third trimester (P less than 0.001) of pregnancy. Ten days after delivery, mean E2 dropped to 13 +/- 2.9 pg/ml and progesterone dropped to 0.56 +/- 0.07 ng/ml in the lactating women; in the nonlactating women, mean E2 level was 100 +/- 44 pg/ml and mean progesterone was 0.63 +/- 0.09 ng/ml. Baseline PRL increased from 27 +/- 15 ng/ml in the third trimester (P less than 0.002). The increased synthesis of PRL with increasing gestation was thought to be due to the stimulatory effects of E2 and progesterone, resulting in hyperplasia of the lactotrophs. In response to TRH, PRL demonstrated a significant increase from the first trimester to the second, with no further increase in the third. Therefore, it appears that the PRL reserve increases only during the first and second trimesters of pregnancy. Ten days after delivery, baseline PRL in response to TRH decreased to levels found in the first and second trimesters. However, the lactating women released less PRL than the nonlactating subjects (P less than 0.01), since PRL is released with each lactating episode which in turn probably reduces the PRL reserve.     

Serum CA 125 levels before, during and after treatment for endometriosis

Objectives: The aim of this study was to assess the treatment of endometriosis with a gonadotropin-releasing hormone (GnRH) agonist in terms of changes to the extent of disease and to CA 125 levels as well as to recurrence during follow-up. Methods: The levels of serum CA 125 were evaluated in 66 patients with endometriosis diagnosed and staged by laparoscopy according to the revised American Fertility Society classification, who received a 6-month course of a GnRH agonist. Serum CA 125 levels were measured before, during (3 and 6 months after the initiation of therapy) and 6 months after cessation of therapy. Results: Patients with minimal and mild endometriosis had significantly higher mean pretreatment values than control subjects in the luteal phase of the cycle or than postmenopausal women (P < 0.05), but the overall mean value was still below 35 U/ml. Levels of CA 125 fell during treatment to those found in normal controls, but rose again after the end of treatment. The sensitivity and specificity of CA 125 were 75% and 83.3%, respectively, and its positive predictive value as a marker of recurrence was 46.36%. Conclusion: These data suggest that CA 125 may be a reliable indicator for monitoring the efficacy of GnRH agonist treatment of endometriosis, but its value as a predictor of recurrence is low, probably due to the suppression of all CA 125 sources such as endometrium, ovaries and implants.     

Hyperprolactinemia: comparison of thyrotropic-releasing hormone and tomography

A group of 95 women with unexplained hyperprolactinemia (over 20 ng/mL) underwent radiologic examination of the sella turcica with hypocycloidal polytomography (N = 58), computed axial tomography (N = 8), or both (N = 29). All patients also underwent a thyrotropin-releasing hormone (TRH) stimulation test, with serum prolactin (PRL) measurement before and 20 and 30 minutes after a 500-micrograms intravenous bolus of TRH. Their PRL responses were compared with those of two control groups, nine normal women in the follicular phase of the menstrual cycle, and 13 women in the first five months of gestation with pregnancy-related hyperprolactinemia. Both control groups exhibited PRL increases with 95% confidence limits at least 200% above baseline levels. In all, 12 patients from the study group also had a normal PRL response (more than a 200% increase) to TRH, and none of these women had tomographic findings consistent with a pituitary tumor. The remaining 83 women all had diminished or absent PRL increases after TRH administration; 46 (55%) of these patients had radiographic evidence of an adenoma, whereas 37 (45%) had no clear signs of a tumor on either polytomography or computed axial tomography. No patient with a baseline PRL level in excess of 60 ng/mL had a normal PRL response to TRH. The results of the study indicate that 1) in patients with PRL between 20 and 60 ng/mL, a normal TRH test can be relied upon to avoid the expense and radiation of tomography (computed axial tomography or polytomography), 2) there is no benefit to be obtained in performing a TRH test in patients with a baseline PRL level over 60 ng/mL, and 3) about 45% of patients with hyperprolactinemia and an abnormal TRH test have a normal computed tomography or polytomography. These patients may have a small adenoma, and thus warrant closer follow-up than patients with a normal TRH test.     

Prolactin hyperstimulation in response to thyrotropin-releasing hormone in patients with endometriosis

In order to clarify the role of hyperprolactinemia as a possible cause of infertility in patients with endometriosis, baseline serum prolactin (PRL) concentrations and the PRL response to thyrotropin-releasing hormone (TRH) stimulation were measured in 14 infertile women with endometriosis and in 13 normal, fertile women. Baseline PRL concentrations were 2-fold greater in the endometriosis group than in normal subjects, but the mean values did not differ significantly. Following TRH administration, a significant increase in peak PRL concentrations was observed in patients with endometriosis (211.5 +/- 34.9 ng/ml) when compared with corresponding values in control subjects (117.1 +/- 14.9 ng/ml, P less than 0.05). This hypersecretory state was selective for PRL because no significant differences between the baseline and TRH-stimulated thyroid-stimulating hormone (TSH) concentrations or total serum thyroxine concentrations were observed. In summary, some infertile women with endometriosis exhibit a greater capacity for PRL secretion than normal women. These results suggest that relative hyperprolactinemia may be responsible for the infertility associated with endometriosis, and that PRL suppression may be indicated in these patients.     

Concentrations of growth hormone, prolactin and thyroid-stimulating hormone in the maternal, fetal and amniotic compartments

GH, PRL and TSH in the maternal, fetal and amniotic compartments were measured by radioimmunoassay in normal pregnant women (group I, n = 16) and patients with anencephalic fetuses (group II, n = 10). The concentrations of GH (20.6 +/- 8.5 ng/ml, mean +/- SD) in cord blood of normal fetuses were significantly higher (p less than 0.001) than those (5.1 +/- 3.5 ng/ml) in anencephalic fetuses. Both maternal PRL levels in group I and group II were lower than their respective cord bloods. The concentrations of PRL (283.1 +/- 127.5 ng/ml) in normal fetuses were higher, but not significantly, than those (199.4 +/- 111.8 ng/ml) in anencephalic fetuses. Also, compared with PRL levels in the maternal and cord blood, those in amniotic fluid were significantly higher (p less than 0.001) in both groups. On the contrary, GH and TSH levels in amniotic fluid were much lower than those in the maternal and fetal blood. The concentration of TSH (10.2 +/- 4.6 microU/ml) in normal fetuses was significantly higher (p less than 0.05) than those (7.1 +/- 3.1 microU/ml) in maternal blood, but not significantly different from those (11.3 +/- 3.6 microU/ml) in anencephalic fetuses. These results suggest that GH, PRL and TSH do not cross human placenta and biosyntheses of these hormones in the maternal and fetal pituitaries are independent.     

Study on the hypothalamic dopaminergic activity in different stages of pregnancy and non-pregnancy

The purpose of this study was to investigate hypothalamic dopaminergic activity in pregnant women after the administration of metoclopramide (MCP), a dopamine receptor blocker, and to investigate the effects of MCP on the placental steroid and peptide hormones, and to clarify the prolactin (PRL) releasing mechanism in the hypothalamo-pituitary axis during pregnancy using dopaminergic agents and TRH. The following results were obtained. The plasma PRL levels following intravenous MCP remained significantly elevated for 180 minutes (p less than 0.001-0.05) in all groups as compared to the control group, but there were no significant differences between early and late pregnant groups, and between pregnant and nonpregnant groups. Therefore, the dopaminergic activity of the hypothalamus remained unchanged during pregnancy as well as in the nonpregnant state. The administration of MCP or a sudden increase in plasma PRL had no effect on the maternal plasma estradiol-17 beta, progesterone, HCG or HPL during pregnancy. PRL release from the pituitary by MCP was suppressed significantly (p less than 0.01) by pretreatment with bromocriptine. PRL releasing activity of MCP 10mg was significantly higher (p less than 0.01-0.05) than that of TRH 500 micrograms in the pregnant women.     

Effect of clomiphene citrate on prolactin and gonadotropin release during GnRH-analog treatment

The capacity of the anterior pituitary to secrete prolactin (PRL) and gonadotropins was evaluated by TRH and GnRH stimulation, followed by metoclopramide (MC) administration 1 hour later, before and after clomiphene citrate (CC) priming in 8 endometriosis patients receiving GnRH agonist analog (Buserelin) therapy for 6 months. GnRH-analog treatment lowered the maximal PRL responses to TRH and MC stimulation in the luteal phase, compared to those of 8 normally menstruating control patients. The LH response to GnRH stimulation was also diminished, indicating pituitary desensitization, while the FSH response remained unchanged. Antiestrogen administration during GnRH-analog treatment further reduced the capacity of pituitary lactotropes to secrete PRL in TRH and MC tests, and it increased the LH response but not the FSH response to GnRH stimulation. These data suggest that CC affects the mechanisms controlling PRL and gonadotropin secretions in hypoestrogenic women after prolonged GnRH agonist analog treatment by different modes of action, the action on gonadotropes being stimulatory and that on lactotropes inhibitory.     

Prolactin and thyroid-stimulating hormone responses to thyrotropin-releasing hormone in cases of hyperprolactinemia with normal and abnormal sella tomograms

An intravenous bolus of 500 micrograms of thyrotropin-releasing hormone (TRH) was used to test prolactin and thyroid-stimulating hormone (TSH) responses in normoprolactinemic patients and in hyperprolactinemic patients with normal and abnormal sella turcica. The prolactin response showed a mean increment of 64.1 +/- 46.3 ng/ml in normoprolactinemic women. In patients with hyperprolactinemia, the mean increment was 14.1 +/- 22.4 ng/ml and 13.8 +/- 33.1 ng/ml for patients with normal and abnormal sella, respectively. The difference in the prolactin response between the normoprolactinemic patients and either group of hyperprolactinemic patients is significant (P less than 0.005). The mean baseline TSH in normoprolactinemic patients is significantly higher than in patients with hyperprolactinemia with normal and abnormal sella. The mean increment of TSH after TRH stimulation is significantly higher in normoprolactinemic patients than in either group of patients with hyperprolactinemia (P less than 0.005). These results suggest an inhibitory action of hypothalamic dopamine on the response of both prolactin and TSH to TRH in patients with hyperprolactinemia. The hypothalamic dopamine mechanism might also be the factor leading to suppression of baseline TSH levels in hyperprolactinemic patients. In addition, these results suggest that patients with hyperprolactinemia, with or without changes in the sella turcica, might have various degrees of the same pathology affecting the lactotropes.     

Evaluation of dynamic pituitary function testing in patients with hyperprolactinemia on diagnosis of pituitary prolactin-secreting adenoma (author's transl)

Thirty hyperprolactinemic women were divided into four group according to radiological and computed tomographic findings of sella turcica as follows; sulpiride-induced (N = 7), functional (N = 6), microadenoma (N = 9) and macroadenoma (N = 8). It was measured the serum basal level of pituitary LH, FSH, PRL, TSH and GH, and the responsiveness to LH-RH, TRH, insulin administration, respectively. These values were compared to that during bromocriptine treatment (5mg/day, 2 weeks). Before and during treatment with bromocriptine, there were not significant changes of basal level of LH, FSH and TSH, and also the responsiveness to LH-RH administration in four group. In pretreatment period, PRL responsiveness to TRH was good in sulpiride-induced and functional groups, but decreased in microadenoma and macroadenoma groups. During bromocriptine treatment period, basal PRL level was significantly suppressed in three groups except sulpiride-induced group, and PRL responsiveness to TRH was good in three groups except macroadenoma group. These findings ae concluded as follows: 1) Mechanism of the disturbance of ovulation in hyperprolactinemia does not closely related to pituitary gonadotroph dysfunction. 2) Decreased PRL responsiveness to TRH (maximal fold increase: under 40%) is of diagnostic value of pituitary adenomas. 3) Difference of PRL responsiveness to TRH during treatment with bromocriptine is distinguishing the microadenoma from macroadenoma.     

Plasma thyrotropin-releasing hormone, prolactin, thyrotropin, and thyroxine concentrations following the intravenous or oral administration of thyrotropin-releasing hormone.

In a further evaluation of the use of oral thyrotropin-releasing hormone (TRH) in puerperally lactating women, a radioimmunoassay for its measurement has been developed. Its concentration in plasma as well as that of prolactin (PRL), thyrotropin (TSH) and thyroxine (T4) were measured following either intravenous or oral administration of TRH. Basal concentrations of TRH in 14 normally cycling women ranged from less than 5 to 17 pg/ml. Two luteal phase studies produced peaks in plasma TRH 5 to 10 minutes after 100 micrograms of TRH administered intravenously with a return to basal concentrations within 2 to 3 hours. In 10 normally menstruating women, ingestion of 10 mg of TRH orally resulted in plasma TRH which peaked at 423 +/- 123 pg/ml (standard error of the mean) at 30-minutes. Plasma PRL, TSH, and T4 also increased and remained slightly elevated at 4 hours. These 8-hour studies were performed in a puerperal lactating woman who had ingested 10 mg of TRH orally twice a day for 7 days prior to blood sampling. TRH concentrations declined throughout each day while TSH rose slightly in the first 1 to 2 hours but remained within normal limits. The prolonged administration of 10 mg of TRH orally twice daily to three puerperally lactating women resulted in elevations in plasma TRH 2 to 3 hours following hormone administration, yet no significant increases in plasma TSH were observed. Both endogenous TRH and TSH were measured before and after 22 nursing events in nine puerperally lactating women. There was no change in the concentration of either substance and all values were similar to those obtained in normally menstruating women.