Lower Luteinizing Hormone Levels Research Articles

Ovarian morphology as a predictor of hormonal values in polycystic ovary syndrome

The objective of this investigation was to correlate the severity of ultrasound abnormality in the ovaries of women suspected of having the polycystic ovary syndrome (PCOS) with their endocrinopathy in an attempt to establish which anatomical abnormalities best predict endocrine dysfunction. There were 90 patients in the study group--all suspected clinically of having PCOS--and 12 control subjects. Of the study patients, 74 were classified ultrasonically as having polycystic ovaries, whereas 16 demonstrated no ovarian abnormality. On ultrasound examination of the ovaries, the follicular size, the number and type of distribution of follicles, ovarian volume and echogenicity of the stroma were assessed. Levels of the following serum hormones were measured: luteinizing hormone (LH), follicle stimulating hormone (FSH), estrone, estradiol, 17 alpha-OH-progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin and testosterone. Calculations were made using these results to obtain the LH:FSH ratio and the free androgen index. Endocrine assessment of these 90 patients demonstrated significantly lower LH levels, lower LH:FSH ratio and lower testosterone levels in the women without ovarian abnormality, compared to those with polycystic ovaries. The women with ultrasound evidence of polycystic ovaries had high. LH levels, a raised LH:FSH ratio and higher testosterone, DHEAS and androstenedione levels than the control subjects. Although a number of multivariate regressions of biochemistry on ovarian morphology were statistically significant, ovarian morphology predicted only a small proportion of the variability in the hormone levels. Multivariate regression models predicting androstenedione and the LH:FSH ratio had the best overall fit with ovarian volume and a rosary follicular pattern as factors, but even for these variables the adjusted R2 value was very low (0.23 for androstenedione and 0.20 for the LH:FSH ratio). It is therefore concluded that, although ovarian morphology may accurately diagnose polycystic ovaries, it does not predict the severity or presence of endocrine dysfunction. Management and prognosis must be determined on an individual basis against the background of a combination of the clinical, biochemical and ultrasound findings.

Hyperinsulinemia in the polycystic ovary syndrome: a clinical, endocrine and echographic study in 240 patients.

In recent years numerous studies have suggested insulin to be an important regulator of ovarian function and hyperinsulinemia to be associated with hyperandrogenism. An oral glucose-tolerance test was carried out in 240 women with polycystic ovary syndrome and, based on its result, 142 of the women (59.2%) were insulin resistant or hyperinsulinemic and 98 (40.8%) were normoinsulinemic. Compared with the normoinsulinemic group, the hyperinsulinemic group had a greater incidence of obesity (52.8 vs. 21.4%), secondary amenorrhea (24.6 vs. 9.2%), androgenic symptoms (85.9 vs. 67.4%) and, in particular, hirsutism with or without acne (71.8 vs. 48.0%). Moreover, the hyperinsulinemic group had significantly higher plasma levels of androstenedione, testosterone, free testosterone and insulin, and lower levels of luteinizing hormone, estradiol and sex hormone-binding globulin.

Endocrine Basis for Two Types of Individual Differences in Lordosis Reflex Intensity

We have identified individual differences in two independent types of lordosis reflex intensity. Overall lordosis reflex intensity, averaged across 9.4 ± 0.99 days (range = 1 - 18 days), differs among cycling individuals and is a biomarker for the rate and pattern of reproductive aging. Although estrogen is necessary to permit lordosis reflex responding and manifests individual differences in progesterone that correlated negatively with the individual variation in overall lordosis reflex intensity; females with intense overall lordosis reflexes had low progesterone throughout the estrous cycle. Independent of their overall reflex intensity, females also displayed individual variation in lordosis reflex intensity on proestrus. Among females that still maintained a cyclic lordosis reflex, those with intense lordosis reflexes on proestrus had high levels of luteinizing hormone (LH) at lights out. Among females that displayed intense lordosis reflexes throughout the estrous cycle (i.e., had entered constant lordosis), those with intense proestrous lordosis reflexes had low levels of LH at lights out on proestrus. Females who had entered constant lordosis tended to have lower overall progesterone than females who still maintained cyclic patterns of lordosis. Thus, constant lordosis. Thus, constant lordosis was identified as an important component of the changes of reproductive aging.

Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring

Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 250 micrograms/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis

We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 +/- 18 to 70 +/- 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of administration of oxytocin in association with gonadotropin-releasing hormone on luteinizing hormone levels in rats in vivo.

Gonadotropin-releasing hormone (GnRH) and oxytocin both stimulate the secretion of luteinizing hormone (LH), although with different characteristics. Therefore, interaction between oxytocin and GnRH in the control of LH may be postulated. We developed models for investigating whether oxytocin can modulate GnRH action on LH in vivo. Pentobarbitone is known to pharmacologically isolate the pituitary from hypothalamic GnRH. We found that after pentobarbitone anesthesia of female rats at proestrus, oxytocin caused a synergistically enhanced LH response to administered GnRH (p < 0.04). In a second series of experiments, female proestrous rats were anesthetized with althesin. This anesthetic allows transport of endogenous GnRH from the hypothalamus to the pituitary. In control animals, which received no exogenous hormone, there was a surge in the mean LH concentration on the evening of proestrus, indicating the presence of endogenous GnRH activity. Thus, the novel model enables detection of interactions of administered hormones with endogenous GnRH. Administration of GnRH plus oxytocin in the afternoon of proestrus caused a reduction (p < 0.01) in the mean level of LH observed in the evening. The reduction was larger than if GnRH alone was administered. Following althesin anesthesia, rats sometimes had low LH levels on the afternoon of proestrus. There was a statistically significant difference between the number of rats that received oxytocin plus GnRH and had low LH levels and the number with low LH levels in the control group (p < 0.02). Neither of the hormones administered alone had a significant effect. Thus, it appears that oxytocin accentuated the effect of GnRH in reducing LH concentrations in althesin-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Large, solitary, luteinized follicle cyst of pregnancy and puerperium

Large, solitary, luteinized follicle cyst of pregnancy and the Puerperium is a rare type of ovarian cyst. The pathogenesis has been related to high gonadotropin levels of pregnancy. Supportive data based on relevant laboratory tests were not available in any previous case reports. The present report describes, for the first time, such a cyst from a 16-year-old Primigravida with both pertinent hormone levels prior to surgery and immuno-histochemical exploration of the lesion. The patient's hormonal profile of absent βHCG and suppressed pituitary gonadotropin levels failed to support a mechanism of abnormal hormonal stimulation as previously postulated. Nevertheless, the stromal hyperthecosis we observed appeared to indicate some degree of luteinizing hormone (LH) stimulation. In view of the low LH levels, such hyperthecosis may reflect a time lag between cause and effect. The results of immunohistochemical studies confirmed the granulosa derivation of the large luteal cells in the cyst wall. By expressing neurophysin, a carrier protein for oxytocin-vasopressin that does not occur in theca cells, these luteal cells reveal a stage of functional activity that is characteristic of the menstrual and early gestational corpus luteum.

Age-related deficits in brain estrogen receptors and sexual behavior of male rats.

Neural estrogen receptors (ER), serum testosterone (T), estradiol (E2) and luteinizing hormone (LH), and masculine sexual behavior were measured in young (5 months) and old (24 1/2 months) Fischer 344 male rats. We found that old intact males, which displayed significantly lower levels of sexual behavior, T, and LH than young intact males, also had lower levels of nuclear ER (ERn) in the amygdala (AMG). The age difference in ER binding did not appear to be a consequence of altered blood E2 levels because circulating E2 did not differ between the two age groups. Gonadectomy eliminated ejaculatory behavior and significantly reduced ERn in young males. When we administered exogenous T to gonadectomized males in doses that approximated levels found in young intact males, we found that sexual performance of old males was stimulated to precastration levels but not to levels found in young males. Moreover, such treatment failed to increase ERn in the AMG of old males to the levels measured in the AMG of young males. These results suggest that there is an association between the inability of T to increase ERn concentration in the AMG and the deficits in sexual performance that are characteristic of old males. Thus, the capacity of neural tissue to bind estrogen, presumably derived from circulating T, may be a limiting factor in the determination of androgen responsiveness in aging males.

Diminished luteinizing hormone release in prenatally stressed male rats after exposure to sexually receptive females

Prenatally stressed (P-S) males show reductions in male sexual behavior, medial preoptic area volume, and levels of circulating testosterone. We examined the luteinizing hormone (LH) response to the presence of a sexually receptive female, a known index of sexual arousal. Adult male offspring from mothers stressed on days 15–22 of pregnancy (thrice-daily exposures to heat, light, and restraint) were implanted with an intraatrial catheter. Forty-eight h later they were placed into test chambers divided by a wire mesh partition; the catheter was extended outside the chamber. Thirty min later a baseline blood sample (time 0 min) was taken and a sexually receptive female was then placed on the side of the partition opposite the male for 60 min. Blood samples were collected 5, 10, 15, 30, 60 min, and 24 h after introduction of the female. Prenatally stressed males exhibited significantly lower LH levels following exposure to the female at each time point, 5 min to 24 h. Furthermore, at no point were P-S males' LH levels significantly increased above baseline levels. These data suggest that attenuations in female-induced LH release are associated with the marked reductions in male sexual behavior characteristic of the P-S male.

Gonadotropin-releasing hormone antagonists with N.omega.-triazolylornithine, -lysine, or -p-aminophenylalanine residues at positions 5 and 6

In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-DPal3 substitutions, where the N omega-amino function of ornithine, lysine, or p-aminophenylalanine (Aph) was converted to the aminotriazolyl (atz) derivatives at positions 5 and 6 with further modifications at positions 7 and 10. The analogues were tested for their ability to bind to pituitary cell membranes, to release histamine in a mast cell assay, to inhibit luteinizing hormone (LH) secretion by castrated male rats or cultured pituitary cells, and to interfere with the ovulation in intact female rats. While the subcutaneous (sc) injection of 50 micrograms of Azaline A (7, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6++ +(atz),ILys8,DAla10]GnRH) dissolved in 0.2 mL of an aqueous media significantly inhibited LH release in the castrated male rat for 24 h, the same dose of Azaline B (11), [Ac-DNal1,DCpa2,DPal3,Aph5(atz),DAph6++ +(atz),ILys8,DAla10]GnRH, inhibited LH release for 72 h. A similar long duration of action was observed for Antide ([Ac-DNal1,DCpa2,DPal3,Lys5(Nic),DLys6(Nic ),ILys8,DAla10]GnRH) but not for Nal-Glu ([Ac-DNal1,DCpa2,DPal3,Arg5,4-(pmethoxybenzoy l)-D-2-Abu6,DAla10]GnRH). In the same paradigm, a 5-fold dilution of the peptide (50 micrograms in 1 mL) and the use of three injection sites rather than one resulted in significantly shorter duration of action for most of the peptides tested. This suggested that long duration of action might be the result of slow release from the injection site(s). In order to investigate this possibility, Nal-Glu and Azaline B were injected intravenously (i.v.) at three doses (10, 50, 250 micrograms) to castrated male rats. At all doses, both peptides significantly lowered LH levels for 8 h. By 24 h, Nal-Glu (250 micrograms) and Azaline B (50 and 250 micrograms) still measurably inhibited LH secretion. Finally, only Azaline B (250 micrograms) was still active at 48 h. These findings demonstrate that subtle structural modifications will yield peptides with different half-lives after iv administration. These findings led us to investigate the effects of other structural modifications on duration of action. We observed that systematic substitutions at positions 7 (NMeLeu) and 10 (Pro9-NHEt, and Gly-NH2) were found to be deleterious. Of interest was the observation that only the DAla10-NH2 substitution led to long duration of action and enzymatic stability under the conditions tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Is an immunoassay available for the measurement of bioactive LH in serum?

An in vitro bioassay for luteinizing hormone (LH) is in our opinion the "gold standard" bioassay. The rodent interstitial cell testosterone assay (RICT) is specific for bioactive LH and very sensitive, accurate, and reproducible. Diverse LH standards consistently display parallel dose-response characteristics. Sera also manifest parallel dose-response characteristics throughout reproductive life, with the exception of basal samples from prepubertal children. This indicates that all known hormones with LH bioactivity have a similar bioactive site. The in vivo bioassays for LH used for calibration of World Health Organization standards are more cumbersome and less precise and accurate than the in vitro bioassay. The ovarian ascorbic acid depletion assay corresponds better than the seminal vesicle weight assay with in vitro bioassay. Variation in the ratio of bioactive to immunoreactive LH (B/I) principally reflects variation in LH immunoassay dose-response characteristics, rather than a change in the bioactive moiety of LH. The varying B/I ratio is due to molecular heterogeneity at multiple levels. Different LH standards contain different proportions of nonbioactive but immunoreactive material. The immunoreactive LH isoforms in serum contain different proportions of bioactive material and the isoform distribution differs with reproductive status. Furthermore, the antibodies comprising the various immunoassay systems detect heterogeneous epitopes on LH, which are not necessarily bioactive. B/I ratio disparities indicate lack of specificity of immunoassays for bioactive LH. Polyclonal antibody-based radioimmunoassay requires the use of purified reagents, including a bioactive tracer, in order to achieve high specificity for bioactive LH. The new generation of monoclonal antibody-based immunometric assays yields results that are lower than, but correlate with, LH measured by the in vitro bioassay. The purest of standards, even a recombinant standard, yields results that differ up to 50% or more from one immunoassay to another. Serum LH levels also differ up to two-fold among assays. The immunometric assays have the advantage of being more sensitive and more specific for low levels of LH in serum than radioimmunoassays, but B/I ratio discrepancies remain great. An immunoassay specific for the bioactive "docking site" of human LH isoforms is still needed.

Assessment of the hypothalamic-pituitary-testicular function in male patients with Wilson's disease.

Sixteen male patients with Wilson's disease were studied to detect potential endocrine dysfunctions. There was no clinical evidence of feminization in any of the patients, and the patient group spanned most pubertal stages. Gonadotropin, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate, androstenedione, estradiol, prolactin, cortisol, thyrotropin, and free thyroxine levels were determined. Low or borderline luteinizing hormone (LH) levels were present in most of the patients. In six of the adult patients, a standard gonadotropin-releasing hormone (GnRH) test was performed. Five of the six patients had blunted LH and follicle-stimulating hormone (FSH) responses to GnRH. Increased androgen levels were found in eight of the patients. Sex hormone-binding globulin was normal in eight of nine tested patients. Three single-dose human chorionic gonadotropin (hCG) stimulation tests of six adult patients showed normal responses. Three other patients who had elevated baseline levels responded with modest increases. Since liver disease is usually associated with decreased androgen levels, it is difficult to account for the elevated androgen levels. Both increased androgen levels and copper accumulation in the hypophysis could be responsible for the blunted GnRH response.

Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate

The relationship of the circulating level of progesterone (P) on the day of human chorionic gonadotropin (hCG) injection to occurrence of clinical pregnancy was examined in 133 leuprolide acetate human menopausal gonadotropin (hMG) in vitro fertilization cycles in women having at least three embryos transferred. Progesterone concentrations greater than 0.5 ng/mL were associated with a significantly lower rate of pregnancy (12/59, 20%) compared with less than 0.5 ng/mL (40/74, 54%, P less than 0.005). The higher P cycles were associated with greater patient age and hMG dose, although these relationships appeared to be indirect. Luteinizing hormone (LH) concentrations remained suppressed. Ovarian stimulation may cause excessive luteinization and an adverse cycle outcome even in the presence of low LH levels. Prospective use of P levels may be helpful to determine optimal hCG timing.

Evidence for two independent pathways in the stimulation of steroidogenesis by luteinizing hormone involving chloride channels and cyclic AMP

The possible role of chloride channels in luteinizing hormone (LH) action on steroidogenesis in rat Leydig cells had been investigated. A chloride channel blocker, SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid), inhibited LH-stimulated steroidogenesis at low (⩽ 1 ng ml ), but not at high (100 ng ml ) LH concentrations. In addition, dibutyryl cyclic AMP- and forskolin-stimulated steroidogenesis was unaffected by SITS. The removal of extracellular chloride potentiated steroidogenesis stimulated by submaximal but not maximal doses of LH. These results suggest that at low levels of LH, steroidogenesis depends on chloride channels whereas with high levels, cyclic AMP is the mediator of LH action.

Plasma luteinizing hormone levels in normal and prenatally stressed male and female rat fetuses and their mothers.

Concentrations of luteinizing hormone (LH) were measured in plasma of fetal and neonatal rats obtained from control mothers and from mothers exposed to stress from Days 14 to 21 of gestation. The regimen of stress used is known to be associated with an abnormal ontogenetic pattern of testosterone secretion from the fetal testes. The overall ontogenetic pattern of immunoreactive LH levels in plasma was similar in male and female rats, and was unaffected by stress. In all groups, LH was low from Days 16 to 20 of gestation, and then rose progressively through birth, i.e. Day 23. However, stressing the mother significantly decreased the already low levels of LH between Days 16 and 20, as indicated by a larger percentage of samples from stressed fetuses of both sexes with LH levels below the limit of sensitivity of the assay. Sex differences in both the control and stressed group became evident only after Day 20 of gestation, with plasma concentrations of females exceeding those of males from Day 21 to 23 post-conception.

Basal gonadotropin hormone release rates during the period of selective follicle-stimulating hormone release in the juvenile female rat

There are situations in which adult female rats release increased amounts of follicle-stimulating hormone (FSH) independent of increased luteinizing hormone (LH) release. This results from, at least in part, a selective increase in the basal FSH release rate. We investigated whether an increase in the basal FSH release rate is contributory to the rise in serum FSH levels which occurs independent of a rise in serum LH levels in the immature female rat. Rats had high serum FSH concentrations on days 7 and 15 after birth, low serum FSH levels on day 23, and low serum LH levels on all three days. In contrast, anterior pituitary gland (APG) FSH and LH concentrations and contents increased from day 7 to day 15 and the contents increased further from day 15 to day 23. Similarly, basal FSH and LH release rates per mg APG or per APG, as assessed by measurement of FSH and LH released into culture medium containing APG(s) from different aged rats, increased from day 7 to day 15 but did not increase further between days 15 and 23. The results indicate that unlike situations observed to date in adult female rats, a mechanism(s) other than an increase in the basal FSH release rate is involved in selective FSH release in the immature female rat.

Thymocyte maturity in male and female hypogonadal mice and the effect of preoptic area brain grafts

Hypogonadal mice with a genetic deficiency of gonadotropin-releasing hormone (GnRH) have low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and gonadal steroids. In this study we found differences from normal mice in many aspects of thymic development. Thymus weights and cellularity were higher in hypogonadal than in normal male mice but lower in hypogonadal than in normal females. Although all normal mice had higher proportions of mature, single staining thymocytes (CD8 + or CD4 +) than seen in hypogonadal mice, there was a sex difference in the basis for this shift. Significantly more double-staining (CD8 +, CD4 +) thymocytes were seen in hypogonadal males than in normal males while both groups had similar single-staining populations. However, in females, both single-staining CD8 + and CD4 + thymocytes were more numerous in normal than in hypogonadal females while numbers of double-staining cells were similar in the two groups. These studies indicate that a mature thymocyte profile may be arrived at through differential effects of reproductive hormones in males and females. When brain grafts containing GnRH cells were used to correct reproductive deficits in hypogonadal mice, there were higher splenocyte counts in males with grafts, a similar trend in females, and a lower ratio of single staining CD4 + to CD8 + thymocytes in all females with grafts vs. all females without, regardless of whether or not the grafts corrected the reproductive hormone status of the recipients, indicating an effect of the graft surgery on the immune system.

The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men

Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100–150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone. One hundred seventy-five patients (70%) had moderate oligospermia (count 5 to <20 million/ml) and 75 patients (30%) had severe oligospermia (count <5 million/ml). Seventy-five moderately oligospermic patients showed significant improvement in the sperm density, total sperm count and motility following mesterolone therapy whereas only 12% showed improvement in the severe oligospermic group. Mesterolone had no depressing effect on low or normal serum FSH and LH levels but had depressing effect on 25% if the levels were elevated. There was no significant adverse effect on testosterone levels or on liver function. One hundred fifteen (46%) pregnancies resulted following the treatment, 9 of 115 (7.8%) aborted and 2 (1.7%) had ectopic pregnancy. Mesterolone was found to be more useful in patients with a sperm count ranging between 5 and 20 million/ml. Those with severe oligospermia (count <5 million) do not seem to benefit from this therapy.

Plasma prolactin and luteinizing hormone profiles during the estrous cycle of the female rat: effects of surgically induced persistent estrus.

Experiments were carried out to investigate the hypothalamic control mechanism for prolactin (PRL) and luteinizing hormone (LH) secretion in the female rat. Anterior medial preoptic nucleus (AMPO) or suprachiasmatic nucleus (SCN) lesions were produced by passing 5-10 microA of direct current (tip negative). Persistent estrus (PE) began as early as 6 days and as late as 30 days after electrolytic lesioning. Blood samples obtained during diestrus, proestrus and estrus revealed well-described profiles of plasma PRL and LH in sham-lesioned animals, indicating that our cannulation and blood sampling procedure had no adverse effects on the plasma hormone levels. Individual sham-operated animals sampled on successive or alternate proestrous afternoons showed precise timing of the PRL and LH surges. However, when a shift occurred in the PRL surge a comparable shift would also occur in the LH surge, indicating a coupling between the mechanisms regulating the PRL and the LH surge. The AMPO-, SCN- or combine-lesioned PE animals exhibited low basal levels of plasma PRL and LH. Small secretory bursts occurred one to three times during the 6-hour sampling periods. Animals with incomplete SCN lesions had plasma PRL titers significantly higher than the other 3 groups. Plasma progesterone levels were significantly lower in the PE animals (p less than 0.01), whereas plasma estrogen levels were not significantly different from proestrous controls. These experiments indicate that during the afternoon of proestrus, the surges of plasma PRL and LH are very precise in the time of onset. Moreover, the mechanisms controlling the surge of PRL and LH are temporally coupled.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroendocrine control of luteinizing hormone secretion and reproductive function in spontaneously persistent-estrous aging rats.

Middle-aged female rats cease to display estrous cycles and exhibit a state of persistent estrus (PE). Under PE and chronic anovulatory conditions, there is a lack of spontaneous luteinizing hormone (LH) surges, but ovulations often occur after the females are caged with males. This study examined the effects of caging and mating with male rats on LH release in PE females, and assessed their reproductive capacity. Young cyclic rats received intra-atrial cannulae, and subsequently were sampled every 90 min during 1400-2130 h on proestrus for plasma LH measurement. PE females were similarly cannulated and sampled. Two days later, these PE rats received an s.c. injection of estradiol benzoate (EB) and were sampled on the following day. While young females exhibited the proestrous LH surge, PE rats maintained low plasma LH levels persistently and were unable to increase LH release after EB administration. On the other hand, when cannulated PE females were caged with fertile males, 92% displayed lordotic responses, and 75% of those sexually receptive PE females exhibited LH surges followed by ovulation. The initiations of the lordotic response and the LH surge both were more rapid in PE females caged with males beginning at 1500 h than at 1400 h. In contrast, when individual PE rats were placed in clean boxes without males, only one of 13 females showed an increase in LH release followed by ovulation. Separate groups of PE rats were mated with fertile males, and subsequently used for counting the number of blastocysts in the uteri on Day 5 of pregnancy and the number of pups delivered at term.(ABSTRACT TRUNCATED AT 250 WORDS)