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SummaryEstrus activity was checked daily in three whitefaced, cross-bred, yearling ewes and jugular blood samples were collected daily during five estrous cycles. Serum prolactin and LH levels were determined by double radioimmunoassays. Prolactin levels were significantly higher during proestrus, (49 mμg/ml) and Day 1 estrus (40 mμg/ml) than during Day 2 estrus (11 mμg/ml), metestrus (15 mμg/ml) and diestrus (14 mμg/ml). LH levels were elevated on Day 1 estrus in only two of the five estrous cycles observed. The mean LH level for all five of the Day 1 estrus observations was 56 mμg/ml. This level was significantly higher than that during Day 2 estrus (1.9 mμg/ml), metestrus (1.6 mμg/ml), diestrus (1.1 mμg/ml) and proestrus (1.4 mμg/ml). These data suggest that the duration of the rise in prolactin levels is longer and precedes the elevated LH value at estrus. Serum prolactin levels did not seem to be correlated with the rise in LH, even though the increase in LH occurs at a time when serum prolactin leve...

In order to test if LH-RH also displays prolactin release-inhibiting activity, synthetic LH-RH was injected into intact diestrous rats and ovariectomized, estrogen-progesterone treated rats. Both groups of rats were pretreated with reserpine in order to increase serum prolactin levels. LH and prolactin were determined by radioimmunoassays. In spite of the fact that LH-RH brought about significant serum LH increase in both groups, no prolactin inhibition was seen. These results indicate that under the conditions of this investigation, LH-RH does not seem to display any prolactin release-inhibiting activity.

The effect of intracarotid (ic) or intravenous infusion of extracts of rat hypothalamus (SME) or brain cortex (CE) on serum prolactin levels was investigated in rats anesthetized with sodium pentobarbital (Nembutal, 35 mg/kg) pretreated with perphenazine (10 mg/kg) and Nembutal, reserpine (0.2 mg) and Nembutal, or subjected to ablation of the medial hypothalamus. Thirty minutes following injection of Nembutal, serum prolaction levels were significantly increased. Injection of perphenazine or reserpine prior to Nembutal injection induced a marked rise in serum prolactin one hour and five hours, respectively, after injection. However, the magnitude of the rise evoked by reserpine was considerably less than that induced by perphenazine and not significantly different from that produced by Nembutal only. Surgical ablation of the medial hypothalamus increased serum prolactin levels 2 hrs after the operation and serum prolactin levels were still elevated 18 days later. In Nembutal-anesthetized rats, infusion of...

SummarySerum prolactin concentrations were determined by radioimmunoassay during estrus cycles in 15 dairy heifers bled by repeated jugular punctures or from a long, indwelling jugular catheter. The method of bleeding was found to influence the serum prolactin concentration and was attributed to nonspecific stress. Further confirmation for the stress effect was provided by a controlled study in other heifers, submitted to specific forms of acute and chronic stress stimuli. In cattle, studies of blood prolactin concentrations under various physiological conditions may be performed only when environmental conditions are carefully controlled.

SummarySynthetic TRH (iv) can significantly increase serum prolactin in proestrous female and in normal and estrogen-primed male rats by 10 min after injection.

Serum prolactin (PRL) concentrations at baseline and after TRH stimulation were determined in 15 healthy women and in 51 premenopausal patients suffering from Gross Cystic Breast Disease. All women were in the luteal phase of the menstrual cycle and patients were divided into three groups according to cyst type at presentation. Basal hormone levels were within the normal range in the control group and in the three cystic breast disease groups. The maximum PRL response to TRH stimulation was significantly higher (p < 0.001) in patients with type I cysts (low Na+/K+ intracystic ratio and apocrine epithelium) than in patients with type II cysts (high Na+/K+ intracystic ratio and flattened epithelium), type III cysts (intermediate Na+/K+ intracystic ratio and mixed epithelium) and in normal women. Serum PRL concentrations corresponding to samples obtained 60 and 90 minutes after stimulation remained higher in the first group of patients. These results led us to consider the existence of an altered central regulation of PRL secretion in patients with type I cysts at presentation.

espanolIntroduccion Diversos estudios han explorado la relacion entre los niveles de prolactina serica, la sintomatologia y la disfuncion cognitiva en individuos con alto riesgo de psicosis y pacientes con un primer episodio psicotico. Sin embargo, la relacion entre tales variables es poco comprendida en el caso de los pacientes cronicos con esquizofrenia. Objetivo Evaluar la relacion entre los niveles de prolactina, el deterioro neuropsicologico y la severidad de los sintomas en pacientes cronicos. Metodo Se evaluo un total de 31 pacientes. El rango de edad fue de 18 a 60 anos, quienes recibieron tratamiento antipsicotico durante un mes como minimo. Los datos se obtuvieron de entrevistas y de la aplicacion de la PANSS y la MCCB. La medicion de la prolactina se realizo con una muestra de 500 microlitros de suero, con una tecnica de quimioluminiscencia. Resultados La muestra estuvo compuesta en su mayoria por hombres (77.4%), con una edad media de 37.65 anos, 13.29 anos de escolaridad y una duracion de la enfermedad de 11.58 anos. No se observaron correlaciones entre los niveles de prolactina y los componentes y subescalas del PANSS. Solo en los pacientes varones se da una correlacion negativa entre los niveles de prolactina con la puntuacion global combinada de la bateria de MCCB y los dominios cognitivos de razonamiento y aprendizaje verbal. Discusion y conclusiones Los hombres diagnosticados con esquizofrenia pueden ser particularmente vulnerables a los efectos negativos de la hiperprolactinemia sobre la cognicion. Teoricamente, estos datos sugieren un efecto protector de las hormonas en las mujeres con esta enfermedad. EnglishIntroduction: several studies have explored the relationship between serum prolactin levels, symptomatology, and cognitive dysfunction in individuals at high risk for psychosis and patients with a first psychotic episode. However, the relationship between such variables is poorly understood in the case of chronic patients. Objective: to assess the relationship between prolactin levels, neuropsychological impairment, and symptom severity in patients with chronic schizophrenia. Method: a total of 31 patients with diagnosis of schizophrenia were evaluated between May and December 2018. The age range was 18 to 60 years, with patients receiving antipsychotic treatment during a month at least. Data was obtained from clinical records, interviews, clinimetry, and with the application of the PANSS and the MCCB battery. For the prolactin measurement, the analysis was performed on a sample of 500 microliters of serum, with a chemiluminescence technique. Results: the sample was comprised mostly by men (77.4%), with a mean age of 37.65 years, 13.29 years of formal education, and disease duration of 11.58 years. No correlations were observed between prolactin levels and PANSS components and subscales. Only in male patients is there a negative correlation was found between prolactin levels with the overall combined score of the MCCB battery and cognitive domains of reasoning and verbal learning. Discussion and conclusions: men diagnosed with schizophrenia may be particularly vulnerable to the negative effects of hyperprolactinemia on cognition. These preliminary data have clinical implications for close monitoring of prolactin and cognitive decline in males with schizophrenia. Theoretically, these data are suggestive of a protective effect of hormones in women with this condition.

The effect of photoperiodic history on the neuroendocrine response to intermediate daylengths (11-13.5 hr of light) was investigated in the male Syrian hamster. The duration of the nocturnal peak of pineal melatonin content was inversely proportional to photoperiod and independent of photoperiodic history. Serum levels of prolactin were lower in animals ex posed to shorter photoperiods. Photoperiodic history had little effect on the response of serum prolactin to intermediate daylengths. Serum luteinizing hormone (LH) concentrations were also lower in shorter photoperiods, but in addition were sensitive to the direction of photo periodic change, so that a single photoperiod could be interpreted as either stimulatory or inhibitory to LH secretion. This effect of photoperiodic history was expressed at intermediate photoperiods with 12-13.5 hr of light. The sensitivity of serum follicle-stimulating hormone (FSH) levels to photoperiodic history was masked by an early onset of photorefractoriness. Testicular size and serum testosterone levels revealed weaker effects of photoperiodic his tory; these were attributed to the dissociation between gonadotrophin and prolactin secretion induced by intermediate daylengths. The contrasting effects of photoperiodic history on the secretion of LH and prolactin may represent the expression of multiple photoperiodic time- measuring systems.

No significant differences were observed between the serum prolactin or serum LH levels of vitamin E-deficient or vitamin E-replete rats during the first 12 days of gestation. It is suggested that pituitary dysfunction is not the cause of the characteristic foetal resorption observed in vitamin E-deficient rats.

To the Editor.— We have just read theJAMAarticle entitled "Cigarette Smoking Associated With Delayed Conception,"1which showed that reduced fertility should be added to the growing list of reproductive hazards of cigarette smoking. In support of their theory, we would like to present the results of a recent population study carried out in Zarate, Argentina, to evaluate cardiovascular risk factors. Among various factors, we measured serum prolactin levels. The results of the evaluation of 73 normotensive men aged 30 to 59 years demonstrated that smoking increases serum prolactin levels significantly (P The relationship between smoking and decreased conception2may be due to the effect of smoking on prolactin secretion. Hyperprolactinemic menhave been reported to have smaller testes and

Long-term bromocriptine treatment was discontinued in thirty-seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty-seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but only three were normoprolactinaemic 3 months after stopping treatment. Two of the seven women had evidence of pituitary tumour regression. After the discontinuation they had nearly normal prolactin levels but during 2 years of follow up the serum prolactin levels slowly increased. In the twenty-seven women with pre treatment prolactin levels below 100 micrograms/I there was no difference between the prolactin levels before starting and 1 month after stopping treatment, while the women with pretreatment prolactin levels above 100 micrograms/l had lower levels after therapy. Bromocriptine treatment seldom results in permanent cure of hyperprolactinaemic amenorrhoea.

In immature male rats, receiving daily injections of bromocriptine (3 mg/kg bw), serum prolactin (Prl) remains low throughout development. In such hypoprolactinaemic males androgen variables are affected: a) the normally low pre-pubertal serum androgen (testosterone, dihydrotestosterone-T, DHT) is considerably increased, in correlation with a precocious development of the testicular Leydig cell population; b) the peri-pubertal rise of androgen is not prevented, but is is followed by significantly lower post-pubertal T, DHT levels, in correlation with moderately reduced Leydig cell counts and with strongly attenuated growth rates of sex accessory organs. Observed alterations of the post-natal androgen pattern cannot be related to LH changes since developmental LH values remained essentially unaltered. Results are in concordance with a marked age-dependent sensibility of androgen variables to a lack of Prl in the developing male.

An abrupt increment in serum prolactin (PRL) levels was demonstrated within 45 minutes of initiation of lunch at 1200 or 1400 h and supper at 1700 h. These observations establish that feeding triggers an acute release of PRL by the hypothalamic-pituitary unit.

A patient with a macroprolactinoma was treated with bromocriptine 15 mg daily. Both the size of the tumour as shown by computed tomography and the serum prolactin concentration decreased over several months but then increased. The dose of bromocriptine was increased to 40 mg daily but tumour growth continued, and the tumour was resected. Production of prolactin by cultured cells was not inhibited by high concentrations of bromocriptine, suggesting that regrowth of the tumour was due to cells resistant to dopamine agonist action. This case of regrowth of a prolactinoma during bromocriptine treatment after an initial reduction in size indicates the need for close surveillance especially of patients whose serum prolactin concentration fails to fall into the normal range with bromocriptine treatment.

To the Editor.— I am a psychiatrist practicing essentially clinical psychopharmacology and I have long been disturbed by the lack of data and studies with respect to the effects of the elevations of serum prolactin produced by antipsychotic agents. Like the treatment of hypertension, the treatment of psychosis generally involves long-term administration of agents that are well known and well demonstrated to raise serum prolactin levels. It would seem time that we begin to take a look at the incidence of carcinomas in patients who have been exposed to these agents for prolonged periods of time. I think it is very likely that when the data are compared it will be discovered that the elevation of prolactin with antipsychotic agents are at least as high if not higher than those found with reserpine, and these agents would probably give a much larger population to study.

Excessive dopaminergic activity in some dopaminergic tracts may be involved in the cause of some types of schizophrenia. We studied serum prolactin levels in newly admitted, unmedicated, psychiatric patients to determine if the prolactin levels in schizophrenic patients might be diminished to reflect increased dopaminergic activity in the tuberoinfundibular tract or the increases associated with psychological stress. Mean serum prolactin concentration was found to be within the normal range in 22 unmedicated, acutely disturbed, newly admitted schizophrenic patients but tended to be elevated in two manic patients and one patient with a severe anxiety state. It may be possible to use these findings to assess the degree of dopaminergic activity of the tuberoinfundibular tract. It appears that the mechanism that causes stress to increase serum prolactin may be abnormal in some schizophrenic patients.

Serum prolactin levels are significantly greater among hypertensive patients receiving reserpine as compared to levels six weeks after discontinuing the treatment ( P ( JAMA 235:2316-2317, 1976)

Prolactin has been thought to play a role in preventing mobilization of tissue water in the neonate. Serum levels of prolactin are low in premature newborns and this may lead to decreased intracellular water, brain shrinkage, capillary bleeding and subsequent IVH. The hypothesis that decreased prolactin levels contribute to development of IVH was studied by our group. Sixteen premature neonates ≤ 32 weeks gestational age with a mean birthweight of 1125 gms were followed prospectively with serial neurosonograms for the development of IVH. Serum prolactin levels by RIA were analyzed from cord blood and on days 1, 3, 7, 10, and 14. Five neonates (m GA = 29.2 wk; m wt 1095 gms) with no IVH or gr I-II IVH were compared to 11 neonates (m GA 29.4 wk; m wt 1139 gms) who developed gr III-IV hemorrhage. Mean serum prolactin levels (ng/ml) were: Serum prolactin levels were comparable between the 2 groups. Our results do not support the concept of a pathogenetic role for prolactin in development of IVH.

72 healthy children, age 1 month to 14 years, were investigated in a cross-sectional study with informed consent of their parents. RIA-determinations of serum-PRL,before as well as 30′, 60′ and 90′ after TRH (200mcg/m2 i.v.) were done.

• The relationship between clinical response of schizophrenic patients to haloperidol and (1) blood levels of the medication, determined by both gas-liquid chromatography (GLC) and radioreceptor (RR) assays, or (2) prolactin response to the medication, was examined in an inpatient study using several fixed doses of haloperidol. Regression analysis disclosed a substantial curvilinear relationship between steadystate GLC-determined plasma haloperidol levels and decrease in Brief Psychiatric Rating Scale (BPRS) Psychosis factor scores; however, no substantial relationship was found between clinical response and RR plasma haloperidol levels or serum prolactin response to haloperidol. Our results suggest that steady-state plasma levels of haloperidol determined by the GLC chemical assay are a better predictor of decreases in BPRS Psychosis factor scores than RR assayed plasma haloperidol levels or prolactin response to haloperidol.

Three cases are described in which hyperprolactinemia occurred as a feature of multiple endocrine adenomatosis, type 1 (MEA-1); enlargement of the sella turcica varied from gross to absent, and serum prolactin (PRL) levels ranged from 21 to 1,000 ng/ml in these cases. Since PRL-secreting pituitary tumors may occur with variable presentation in MEA-1, periodic measurements of serum PRL levels should be carried out to detect this abnormality. ( Arch Intern Med 138:1807-1808, 1978)

To the Editor.— We read with interest the article by Spark and co-workers (1982;247:311) about the effects of bromocriptine on the size of prolactin-secreting, human-growth-hormone-secreting and nonsecretory pituitary tumors and would like to make a comment about some of the issues raised therein. During the past five years, we administered bromocriptine (2.5 to 15 mg/day) for two to 46 months to 26 patients (12 females and 14 males) with prolactin-secreting pituitary macroadenomas with computed tomographic (CT) scan controls before, during, and after bromocriptine therapy. Eighteen of them had previously undergone pituitary surgery (by transsphenoidal or transfrontal route), telecobaltotherapy, or both, while eight had never been treated before. In our experience, the normalization of prolactin levels was not always related to the reduction of the tumor mass: in fact, bromocriptine normalized serum prolactin concentration in 19 cases (73%), while a shrinkage of the adenoma was documented at CT scan in only

A 30-year-old woman had galactorrhea and secondary amenorrhea, along with symptoms, signs, and laboratory findings of primary hypothyroidism. Serum prolactin and thyrotropin (TSH) levels were elevated. After initiation of thyroid hormone replacement, serum TSH and prolactin levels fell progressively into the normal range. Along with these changes, the patient noted a return of normal menstrual function and the galactorrhea disappeared. ( Arch Intern Med 138:1411-1412, 1978)

We prospectively studied serum prolactin (PRL) elevation after different types of documented seizures in 17 patients. Marked PRL elevations above normal and above three times baseline were seen at 15 or 30 minutes after 20 of 25 (80%) generalized tonic-clonic, 13 of 30 (43%) complex partial, and 1 of 10 (10%) simple partial seizures. Although marked postictal PRL elevation is a sensitive indicator of recent epileptic seizures, a normal 15- or 30-minute postictal PRL level does not exclude an epileptic seizure.

Hyperprolactinemia was demonstrated in eight of nine patients with clinical evidence of pituitary tumors without acromegaly or Cushing syndrome. Hourly sampling for 24 hours disclosed elevation of serum prolactin concentrations, whereas, measurable serum growth hormone levels were found rarely. Although eight of these patients were hypersecreting prolactin, only four of them were lactating. Prolactin secretion was characterized by moderate hourly fluctuations of serum levels and absence or blunting of the normal sleep-related augmentation of secretion. Patients with the highest serum prolactin concentrations tended to have the largest pituitary tumors, as indicated by pneumoencephalography. In two patients followedup with serum prolactin determinations after treatment, a fall in serum prolactin concentrations correlated with clinical improvement. Future study will hopefully establish the value of serum prolactin determinations in following tumor growth before and after pituitary ablative therapy. ( Arch Intern Med 136:40-44, 1976)

469 SERUM PROLACTIN IS ELEVATED IN CHILDREN WITH CONGENITAL GROWTH HORMONE DEFICIENCY ASSOCIATED WITH PERINATAL COMPLICATIONS

To study the effects of beta-endorphin in chronic schizophrenia, nine male patients participated in a double-blind crossover comparison of a single intravenous 20-mg injection of beta-endorphin and saline. Bolus injection of beta-endorphin from an albumin-coated syringe produced markedly higher plasma concentrations than did slow intravenous infusion from a non-albumin-coated syringe. Beta-endorphin intravenously injected in nine patients produced a statistically significant increase in serum prolactin levels. In one patient, both 10 mg of morphine sulfate and 20 mg of beta-endorphin produced similar increases in the alpha power of the EEG. In eight patients, beta-endorphin administration was associated with a statistically significant but not clinically obvious improvement in schizophrenic symptoms.

In vitro, prolactin secretion but not release is influenced by media Ca. Prolactin homeostasis in VLBW infants and effect of neonatal HC on secretion and release of prolactin are unclear. In 6 preterm AGA neonates, birthwt. 1050 ± 96 gms(mean ± sd), gestation < 32 wks, we studied the theses: 1)serum prolactin would be high; 2)serum Ca