Blunted prolactin response to exogenous luteinizing hormone releasing hormone in superovulated women

To investigate the prolactin (PRL) response to luteinizing hormone releasing hormone (LHRH) in superovulated cycles, eight normally ovulating women were studied in two cycles, i.e. a spontaneous (control) and a cycle treated with 'pure' follicle stimulating hormone (FSH) (225 IU/day). LHRH was given to the women i.v. (a single injection of 100 micrograms) in the late follicular phase of both cycles. The oestradiol levels (mean +/- SEM) at the time of the LHRH challenge were 635 +/- 31 and 1707 +/- 225 pmol/l respectively (P less than 0.001). The size of the leading follicle was similar in both cycles. Basal PRL levels (mean +/- SEM) on the day of the LHRH experiment were significantly higher in the FSH (250 +/- 31 microIU/ml) than in the spontaneous cycles (133 +/- 15 microIU/ml. P less than 0.05). In the latter cycles, LHRH induced a significant increase in serum PRL and LH levels, while the FSH cycles, the prolactin (PRL) response to LHRH was blunted and LH response markedly attenuated. We conclude that superovulation induction stimulates basal but suppresses LHRH-induced PRL release. It is suggested that basal PRL secretion is LHRH-independent and the suppressing effect is mediated via previously described paracrine interactions between the gonadotrophs and lactotrophs and/or through ovarian inhibitory substances.     

Pre-ovulatory granulosa cells of infertile women with endometriosis are less sensitive to luteinizing hormone

PROBLEM: Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic-pituitary-ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis. METHOD OF STUDY: Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls. RESULTS: Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58-9.24) versus 0.33 (0.28-0.72) ng/mL, P = 0.019], indicating reduced sensitivity to LH. CONCLUSIONS: In women with endometriosis, granulosa cells were less sensitive to LH stimulation. This provides further evidence for primary ovarian dysfunction as a significant contributory cause of the associated subfertility.     

Altered luteinizing hormone pulsatility in infertile patients with idiopathic oligoasthenozoospermia

In a previous study, we demonstrated that oligoasthenozoospermic(OAZ) patients had two types of testosterone response to humanchorionic gonadotrophin (HCG) administration: group 1 (OAZ-1)had an altered, monophasic (no first peak) response, and group2 (OAZ-2) had a normal biphasic response. The objective of thepresent work was to study the luteinizing hormone (LH) pulsatilityin OAZ-1 compared with both OAZ-2 and men of proven fertility(PF), in order partly to determine the possible aetiology ofthe blunted acute testosterone response to HCG in these patients.LH pulsatility was measured in 10 PF, 10 OAZ-1 and 10 OAZ-2patients, in blood samples taken every 5 min for 6 h in PF,and for 4 h in OAZ patients. LH values were determined by atime-resolved immunofluorometric assay. Frequency and amplitudeof the LH pulses were determined by a computer program. LH pulsefrequency, expressed as pulses/4 h, was significantly lowerin OAZ-1 (1.5 ± 0.97) than in PF (2.4 ± 0.63)and OAZ-2 (2.4 ± 0.84) patients. In six OAZ-1 and twoOAZ-2 patients, LH pulsatility was diminished, as they showedless than two pulses/4 h. No statistically significant differencesin LH pulse amplitude were found. These results, together witha higher number of OAZ-1 cases found with decreased LH pulsatility,suggest that, at least in a subset of these men, quantitativeand/or qualitative alterations of LH secretion might have occurred.     

A study on the effects of interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone, follicle-stimulating hormone, prolactin and thyroid-stimulating hormone levels in normal man serum.

The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone.     

Seasonal, menstrual and circadian secretions of melatonin, gonadotropins and prolactin in women

In order to evaluate the role of the pineal gland in human reproduction, day- and night-time concentrations of serum melatonin, FSH, LH and prolactin were measured by radioimmunoassays on various days of the menstrual cycle during summer (average daylight 22 h) and winter (daylight 5 h) in healthy females (n = 12) from northern Finland (65 degrees N). A multifactorial analysis of variance showed that, in addition to the well-established increases of gonadotropins at midcycle and melatonin and prolactin at night, there was a significant effect of season on the serum levels of melatonin and LH. Night-time serum melatonin levels on cycle days 2 and 10 were 27% and 49% (P less than 0.05 and less than 0.01) higher in winter than in summer. Night-time serum LH levels at midcycle were 76% (P less than 0.05) higher in summer than in winter. There were no significant effects of season on the serum levels of FSH, prolactin, day-time melatonin or LH outside the mid-cycle. Neither were there any significant effects of the day of the menstrual cycle on the serum melatonin levels. It is possible that in winter the high levels of melatonin in the follicular phase have an inhibitory effect on the serum LH levels. In summer the melatonin levels are lower and perhaps less inhibitory on the secretion of LH, resulting in the stimulation of the reproductive competence in human females.     

Human prolactin release induced by follicle stimulating hormone, luteinizing hormone and human chorionic gonadotrophin

Plasma prolactin levels rise in stimulated cycles. To clarifythe effects of gonadotrophin on the lactotrophs, three studieswere performed. First, plasma concentrations of prolactin duringclomiphene citrate (CC)-human menopausal gonadotrophin (HMG)-humanchononic gonadotrophin (HCG) treatment of women enrolled forin-vitro fertilization (IYF) were compared with those duringHMG-HCG administration while under pituitary suppression witha gonadotrophin releasing hormone (GnRH) analogue (buserelin).Women suppressed with buserelin had higher basal levels of PRLin plasma (14.4 ± 4.3 nglml versus 6.9 ± 1.4 ng/ml,P<0.001). Only buserelin-suppressed women showed a significantrise in plasma prolactin before HCG administration, while bothpatient groups had marked prolactin peaks after HCG injection.This peak was higher in the buserelin group (71.9 ± 50.7ng/ml versus 52.6 ± 29.7 ng/ml). The second study showedthat plasma levels of prolactin of 6 post- menopausal womenwere significantly increased 48 h after an injection of 5000IU HCG, i.m. (24.9 ± 17.4 ng/ml versus 12.4 ±6.2 ng/ml P<0.05). Third, plasma prolactin was studied in5 women over 30 days after surgical castration. An upward trendwas observed similar to that of endogenous gonadotrophin, withthe change in prolactin values closely correlating with thechange in concentrations of follicule stimulating hormone (P<0.005).All these findings suggest that human gonadotrophins stimulatelactotrophs.     

Effect of Thymomodulin on luteinizing hormone, prolactin and testosterone in male rats.

The effect of Thymomodulin (TMD), a calf thymus derivative, on luteinizing hormone, prolactin and testosterone was studied in male rats after acute and chronic treatment. The results showed that the stimulatory action on prolactin and testosterone secretion after acute (prolactin) or one month chronic (testosterone) treatments completely vanished during six month chronic administration. No effect was observed on luteinizing hormone after acute or chronic treatment.     

Effect of shift work on the night-time secretory patterns of melatonin,prolactin, cortisol and testosterone

Summary In a study of the internal desynchronization of circadian rhythms in 12 shift workers, 4 of them, aged 25–34 years, agreed to be sampled every 2 h during their night shift (0000 hours to 0800 hours). They were oil refinery operators with a fast rotating shift system (every 3–4 days). We found marked changes in the secretory profiles of melatonin, prolactin and testosterone. Melatonin had higher peak-values resulting in a four-times higher amplitude than in controls. With respect to prolactin and testosterone, peak and trough times were erratic and the serum concentrations were significantly decreased in shift workers. Serum cortisol presented a decreased rhythm amplitude together with higher concentrations at 0000 hours in shift workers. This study clearly shows that fast rotating shift-work modifies peak or trough values and rhythm amplitudes of melatonin, prolactin, testosterone and cortisol without any apparent phase shift of these hormones. Whether the large rhythm amplitude of melatonin may be considered as a marker of tolerance to shift work, as reported for body temperature and hand grip strength, since it would help the subjects to maintain their internal synchronization, needs further investigation.     

Thyroid antoantibodies and the response to thyrotropin releasing hormone in patients with subclinical hypothyroidism.

AIM--To evaluate the clinical usefulness of the thyrotropin releasing hormone (TRH) test and estimation of thyroid autoantibody concentrations in patients with borderline raised thyroid stimulating hormone (TSH). METHODS--The records of 34 consecutive patients with persistent borderline increased TSH (4.4-9.9 mU/l) referred to the Medical Investigation Unit were reviewed. The response of patients with thyroid autoantibodies to the TRH test was compared with that of patients with a negative antibody screen. RESULTS--Eleven (44%) of 25 patients with positive anti-thyroid microsomal and/or thyroglobulin antibody tests and three (33%) of nine patients with a negative antibody screen had hypothyroid responses to TRH. Neither age nor sex affected the response to TRH. Basal TSH alone was poorly correlated with these indices. Twelve (35%) patients who had elevated basal TSH had a normal response to the TRH test. CONCLUSION--Patients with positive or negative thyroid autoantibodies and an exaggerated response to the TRH test should be regarded as hypothyroid and treated with thyroxine. Patients with positive thyroid autoantibodies and normal TSH response may subsequently develop hypothyroidism and should be given long term follow up.     

Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women

The role of dopamine and opiates in the suckling-induced suppressionof gonadotrophin secretion and prolactin release was investigatedduring lactational amenorrhoea in fully breastfeeding womenat 12 weeks post-partum. A total of 26 women, 20 using non-steroidalmethods of contraception and six using the progestogen-onlypill, Noriday (POP), breastfed their babies on demand at a frequencyof 3.6 ± 0.2 suckling episodes during the 8 h study periodwhile blood samples were collected at 10-min intervals. Fivehours after the start of sampling six women were given the dopamineantagonist metoclopramide (10 mg, i.m.) while four women receivedsaline. In a second experiment, six women using nonsteroidalcontraception and three women on the POP received an i.v. infusionof the opiate antagonist naloxone (1.6 mg/h) for 2 h, whilefour women using non-steroidal contraception and three womenon the POP were infused with saline. Two hours after the i.m.injection or start of infusion all women were given an i.v.injection of 10 µg gonadotrophin releasing hormone (GnRH)and samples were collected for a further 1 h. All samples wereassayed for luteinizing hormone (LH), follicle stimulating hormone(FSH) and prolactin. Plasma concentrations of oestradiol were<60 pmol/l in all women and they remained amenorrhoeic forat least 10 weeks after the study. Pulsatile release of LH wasonly observed over the 5 h pre-treatment period in 10 of the20 non-steroid taking women (1–3 pulses/5 h), and in oneof the six women (1 pulse/5 h) on POP. Treatment with metoclopramidecaused a substantial (29-fold) increase in prolactin over baseline,7.4 times the maximum released in response to suckling. Therewas no effect of metoclopramide on the pattern of release ofLH or FSH or the response to GnRH. Infusion of naloxone in womenusing either non-steroidal contraceptives or progestogen-onlypill did not affect prolactin release. Naloxone infusion didnot affect LH or FSH in women using nonsteroidal contraceptives,but caused a small but significant (P < 0.05) increase inboth LH and FSH in women taking the progestogen-only pill. Therewas a significantly greater release of LH and FSH after GnRHin all women after naloxone infusion. These results in breastfeedingwomen during lactational amenorrhoea confirmed that sucklingsuppresses the pulsatile release of LH but not through a dopaminergicpathway, showed that prolactin remains under dopaminergic controlduring human lactation, but suckling does not appear to affectprolactin secretion via an opiate pathway and indicated onlya minor, if any, role for opiates in the sucklinginduced suppressionof GnRH/gonadotrophin secretion but a potential, previouslyunreported, effect of opiates in reducing pituitary responsivenessto GnRH.     

The 24 h pattern of pulsatile luteinizing hormone, follicle stimulating hormone and prolactin release during the first 8 weeks of lactational amenorrhoea in breastfeeding women.

In women, breastfeeding results in a variable period of ovarian inactivity which is apparently related to suppression of the normal pulsatile release of luteinizing hormone (LH). However, pulse profiles had only been studied during the daytime. Since resumption of pulsatile LH secretion during puberty is initiated at night, the present study determined the pattern of pulsatile LH secretion in relation to that of follicle stimulating hormone (FSH) and prolactin, and suckling and ovarian activity at 4 and 8 weeks postpartum in 20 fully breastfeeding women with lactational amenorrhoea. Blood samples were withdrawn at 10 min intervals for 24 h from 0900 h to 0900 h at either 4 weeks (n = 9) or 8 weeks (n = 11) postpartum, while the mothers and babies continued their normal pattern of suckling activity. At 4 weeks postpartum, no LH pulses occurred over 24 h in six of the nine women while one (n = 1) or two (n = 2) LH pulses occurred in three of the nine women. In contrast, LH pulses were present in nine of the 11 women at 8 weeks postpartum. The pulse frequency varied considerably from two to eight pulses over the 24 h and there was no influence of the time of day or sleep on the time of the pulse release. Lactational amenorrhoea was maintained for at least 10 weeks afterwards and there was no relationship between the time of resumption of ovarian activity and the presence or absence of pulsatile LH secretion at 4 or 8 weeks postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia

We studied the growth hormone (GH) response to GH-releasing hormone (GHRH) and the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in four groups of patients with dementia and examined whether GH and TSH secretion is altered in patients with Alzheimer's disease. The four groups included those with Alzheimer's disease (n=28), parkinsonism with dementia (n=10), progressive supranuclear palsy with dementia (n=10), and dementia of vascular origin (n=28). The results showed no differences among the four groups in GH response to GHRH (12.2 ± 2, 10.7 ± 2, 8.9 ±1.1, and 9.9 ± 1.9 g/ml, respectively); there was no correlation between GH response to GHRH and sex, stage of the disease, or cerebral atrophy. The proportion of patients with exaggerated, normal, or lower GH response was similar in the four groups. There were also no differences among the groups in terms of TSH response to TRH (9.2 ±0.9, 11.1 ± 1, 11.1 ± 1, and 10.3 ± 1 mU/ml, respectively), nor was there a correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy, or GH response to GHRH. The proportion of those with exaggerated, normal, or lower TSH response was similar in the four groups. Cerebrospinal somatostatin levels were similar in Alzheimer's disease and vascular dementia patients. These findings indicate that neither GH response to GHRH nor TSH response to TRH provides a useful diagnostic adjunt in Alzheimer's disease patients.Abbreviations AD Alzheimer's disease - PD parkinsonism with dementia - PSP progressive supranuclear palsy - VD dementia of vascular origin - GH growth hormone - GHRH growth hormone releasing hormone - TRH thyrotropin releasing hormone - TSH thyroid stimulating hormone Correspondence to: J.M. Gomez     

In vitro pituitary prolactin, growth hormone and follicle stimulating hormone secretion during sexual maturation of female rats primed with melatonin

The influence of in vivo melatonin administration on in vitro pituitary follicle stimulating hormone (FSH), growth hormone (GH) and prolactin secretion, as well as the possible influence of dopamine (DA) were evaluated in prepubertal (31-day-old), pubertal (33-day-old) and adult female rats at diestrus phase of the sexual cycle. The in vitro pituitary hormone secretions were evaluated at basal rate for the first hour of incubation only, in Krebs Ringer phosphate (KRP) (I1) and after a second hour of incubation with KRP (I2) or with KRP+DA (I2 plus DA). I1PRL secretion was significantly higher in 33-day-old control and melatonin treated (MEL) rats as compared to I2 periods. However, in 31-day-old rats I1 secretion was higher than in the I2 or I2+DA periods, in MEL rats. In vitro GH secretion was significantly higher at I1 than during I2 periods in the control 31- and 33-day-old groups, but not in MEL rats. The only significant effect of DA was the elevation of GH in prepubertal MEL rats. In vitro FSH release was increased by melatonin in 31- and 33-day-old female rats. No differences in PRL, GH and FSH secretion were found in adult rats. In conclusion, the results show that melatonin effects upon in vitro pituitary gland activity are reproductive-stage-dependent modifying the secretory capacity of the lactotrop, gonadotrop and somatotrop during prepubertal and pubertal ages but not in adult rats studied at a quiescent phase of the sexual cycle.     

Total cortisol levels are reduced in the periovulatory follicle of infertile women with minimal-mild endometriosis

PROBLEM: To measure and compare concentrations of total and free glucocorticoids with oocyte fertilizing capacity in the follicular fluid (FF) of women with minimal-mild endometriosis and tubal damage. METHOD OF STUDY: Follicular fluid was collected from individual periovulatory follicles during oocyte retrieval for in vitro fertilization (IVF) in natural cycles. Total and free levels of cortisol and cortisone were measured using specific radioimmunoassays after chloroform extraction. RESULTS: Cortisol concentrations in women with minimal-mild endometriosis were significantly lower compared with controls (women with tubal infective damage) (258 versus 328 nmol/L, P < 0.02). There was no correlation between total or free concentrations of cortisol or cortisone and the fertilization capacity of the oocyte. CONCLUSIONS: Total cortisol levels are lower in the follicles of women with endometriosis. Our findings provide further evidence of follicular dysfunction contributing to the subfertility associated with minimal-mild endometriosis.     

Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage

Polycystic ovary syndrome is associated with hypersecretionof luteinizing hormone (LH) which has been implicated in theaetiology of early pregnancy loss. Although 82% of women withrecurrent early loss have polycystic ovaries on ultrasound imaging,random serum LH concentrations are normal. In the present study,we have obtained further information from serial samples concerningthe cyclical patterns of gonadotrophin and sex steroid secretionin these women. Twenty-one women with recurrent early pregnancyloss and 10 multiparous controls were investigated; 81% of themand one of ten control subjects had polycystic ovaries. Meanmid-follicular and mid-luteal serum LH and follicle stimulatinghormone (FSH) levels were similar in both groups. Seventeenwomen with pregnancy loss had either raised urinary LH excretionor a premature LH surge; one control subject had a prematureLH surge. Total LH excretion during the cycle and mean follicularphase serum testosterone was significantly greater with earlypregnancy loss than in the control group, the difference inLH being greatest in the early luteal phase. Urinary oestrone-3-glucuronideexcretion was raised in the early luteal phase of the cyclein the group with early pregnancy loss; there was no differencebetween the groups in pregnanediol-3-glucuronide excretion.These data demonstrate abnormalities in LH secretion in 81%of women with recurrent fetal loss. Inappropriately raised LHlevels may have adverse effects on the developing oocyte orendometrium either directly, or indirectly by causing an elevationin testosterone and oestrogen levels.     

Release of prolactin and luteinizing hormone by histamine agonists in ovariectomized,steroid-treated rats under ether anesthesia

Responses to histamine agonists administered intraventricularly under ether anesthesia were analyzed to evaluate receptor mediation in histamine stimulation of prolactin and LH release in ovariectomized, estradiol-progesterone-treated rats (OVX-E2P-treated rats). Prolactin release was markedly increased by the H2-histamine agonists, 4-methyl histamine and Dimaprit. These effects were antagonized by metiamide, an H2-blocking agent. The H1-histamine agonist, 2-(2-pyridyl)ethylamine (PEA) in high doses released prolactin and its effect was partially prevented by metiamide. Mepyramine, and H1-antagonist, did not exert any effect on the release of prolactin enhanced by the histamine agonists. LH release was significantly increased after 4-methyl histamine administration. Its effect was weak and was blocked by metiamide. Neither Dimaprit nor PEA exhibited action on plasma LH levels. The results obtained with histamine agonists suggest that histamine evokes prolactin release in OVX,E2P-treated rats through H2-receptors. At present, conclusions on H2-receptor mediation in LH release induced by histamine cannot be drawn from these results. The above-mentioned data, however, conclusively discard a significant participation of H1-receptors.     

Interactions of oestrogens and hours of sleep on cortisol,FSH, LH,and prolactin in hypogonadal women

The effects of conjugated oestrogens 0.625 mg and placebo on adrenal and pituitary hormones were compared in 10 postmenopausal women during their sleep by means of a double blind prospective crossover study. On placebo, the women had nocturnal variations in LH, prolactin and cortisol concentrations. However, oestrogen administration selectively blunted LH and prolactin changes, but not the rise in cortisol.