Rise In LH Levels Research Articles

Gonadotrofinas hipofisiarias séricas durante el ciclo menstrual, medidas por radioinmunoensayo

Empleándose técnicas de radioinmunoensayo, se han determinado los niveles de LH Y FSH en suero a través del ciclo menstrual, en 15 ciclos de 12 mujeres normales en edad reproductiva (23 a 35 años de edad). Once mujeres presentaron una gran elevación en los niveles de LH en la mitad del ciclo (días 12 a 21). Seis de estas mujeres también presentaron elevación significativa en los niveles de FSH, coincidiendo con la de LH, y una mujer presentó una elevación de FSH un día después de la elevación en LH. El más alto nivel de LH alcanzado osciló entre 33.5 y 160 mui/ml. IRP-HMG-2 (promedio ± es 90.8 ± 10.9) y el de FSH osciló entre 26.5 y 44.0 mui/mI. (promedio ± es 31.6 ± 2.5). Los niveles de LH y FSH durante la fase folicular (LH 19.5 -1- 3.2 y FSH 16.3 ± 2.1) resultaron más elevados que en la fase luteínica (LH 9.5 ± 3.5 FSH 7.7 ± 3.1). La relación FSH/LH fue menor durante la fase ovulatoria (0.35) que durante los primeros (0.83) y últimos días (0.81) del ciclo.

Effects of oral buserelin on urinary LH secretion in male infants

In recent years, several potent gonadotropin-releasing hormone (GnRH) analogues have become available for female contraception and one of them (buserelin) has been tested in lactating women. However, the possible effects on infants due to the transference of the analogue through breast milk have not been studied. The present work evaluated the effect of oral buserelin on urinary LH secretion in male infants. A total of 19 healthy full-term boys (aged 2–4 months) were included in the study. Infants received orally a single dose of a GnRH agonist mixed with breast milk. Urine samples were collected prior to, and 4–6 and 24 h after treatment for LH measurement. The results disclosed a significant increase in LH urine level in the sample taken 4–6 h after buserelin administration. Twenty-four hours after GnRH agonist ingestion, the LH level returned to baseline level. The present study demonstrated that GnRH analogue administered orally to infants escapes from gastrointestinal inactivation and induces a significant rise in LH levels 4–6 h after treatment.

Inhibition of the LH surge in cyclic rats by stress is not mediated by opioids.

The effects of intravenous (iv) administration of the opioid antagonists naloxone and naltrexone on the restraint-induced suppression of the pro-estrous LH surge were studied in cyclic female rats. To minimize stress during repeated blood sampling, the rats were provided with a jugular vein cannula. Restraint stress for 6 hrs starting at t = -1 h (the onset of the LH surge being at t = 0 h) caused a suppression of LH levels (including peak height) during the period of the LH surge. Repeated naloxone injections, given 3 h (1 mg), 4 h (0.5 mg) and 5 h (0.5 mg) after the onset of the LH surge, did not affect the restraint-induced inhibition neither did pretreatment with 1 mg naloxone at t = -75 min (i.e. 15 min before application of restraint). Naltrexone (2 mg) administered at t = -15 min induced higher plasma LH levels at t = -6 min. When rats were subsequently subjected to restraint for 5 hrs starting at t = -5 min, the restraint-induced inhibition of surge levels of LH was not affected. The results indicate that withdrawal of opioid activity in cyclic female rats before the presumed onset of the LH surge results in a premature rise of LH levels. This is in accordance with the notion that LH levels prior to the surge are under tonic inhibition of endogenous opioid peptides (EOP). In addition, the data show that opioid receptor antagonism during or before application of restraint does not alter the restraint-induced suppression of the LH surge. It is therefore concluded that EOP do not mediate the inhibitory effect of restraint stress on the LH surge in cyclic rats.

Blockade of Singular Follicle-Stimulating Hormone Secretion and Testicular Development in Photostimulated Djungarian Hamsters (Phodopus Sungorus) by a Gonadotropin-Releasing Hormone Antagonist1

Photostimulated male Djungarian hamsters following placement in a long-day photoperiod exhibit a characteristic rise in serum FSH levels that occurs in the absence of a simultaneous rise in LH levels. It is not known whether this singular FSH secretion is dependent upon a differential responsiveness of the gonadotrophs to the pattern of pulsatile GnRH release or is instead driven by a GnRH-independent mechanism. We have assessed the GnRH dependence of this singular FSH secretion by testing the ability of a potent GnRH antagonist (GnRHa: WY-45760) to block FSH and testicular responses to photostimulation. Photoinhibited hamsters were transferred from a short-day (6L:18D) to a long-day photoperiod (16L:8D). Hamsters received two daily injections of a GnRH antagonist or vehicle (VEH). After 0 (short day), 3, 5, 10, 30, or 40 days the hamsters were killed; plasma was assayed for FSH, LH, and testosterone (T), and testes weights were recorded. Testes were sectioned and analyzed for tubular development. In VEH-treated animals, testicular weights increased after photostimulation, reaching mean values of 514 mg by 30 days. Treatment with GnRHa resulted in a significant (p < 0.01) attenuation of testicular growth after 30 days of photostimulation (mean testes weight = 110.1 mg). In VEH-treated hamsters there was a rapid increase in FSH levels after photostimulation that became significant by 5 days and peaked at 10 days. In the GnRHa-treated group, however, these FSH increments were completely blocked at 5 days and significantly reduced at 10 days compared to the values in the corresponding VEH-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization

To determine if women who previously had demonstrated poor ovarian responsiveness during ovulation induction for IVF would obtain an improved follicular response by the administration of microdoses of GnRH agonist (GnRH-a). Prospective evaluation using the same patients' previous assisted reproductive technology cycles as historic controls. Large military tertiary care center. Thirty four patients who were low responders (peak E2 < 500 pg/mL [conversion factor to SI unit, 3.67]) during ovulation induction with luteal phase GnRH-a suppression followed by exogenous gonadotropins. Follicular phase administration of 20 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and supplemented with exogenous gonadotropins beginning on cycle day 5. Paired analysis of initial E2 response, peak E2 level attained, number of follicles > or = 16 mm, duration of stimulation, ampules of gonadotropins required, late follicular LH levels, number of mature oocytes retrieved, and fertilization rates. Ovarian responsiveness was enhanced during the microdose GnRH-a stimulation cycle when compared with the previous stimulation cycle. Specifically, the patients had a more rapid rise in E2 levels, much higher peak E2 levels, the development of more mature follicles, and the recovery of larger numbers of mature oocytes at the time of retrieval. None of the patients had premature LH surges as evidenced by a significant rise in LH levels or a significant decline in E2 levels. There were no differences in the fertilization rates. Microdose GnRH-a administration beginning in the early follicular phase may result in an augmented ovarian response when compared with traditional GnRH-a-exogenous gonadotropin stimulations. Additionally, it may decrease gonadotropin requirements while effectively preventing premature LH surges.

Luteinizing hormone-releasing hormone terminals in the median eminence of rats undergo dramatic changes after gonadectomy, as revealed by electron microscopic image analysis

Despite intense investigation, the modulation of LHRH release, essential to reproduction, is not fully defined. In this study we investigated whether dynamic transformations of individual LHRH terminals in the median eminence of the hypothalamus occurred as a function of gonadectomy in rats, using immunocytochemistry and electron microscopy with quantitative image analysis. One day after castration, the distance between LHRH terminals and the basal lamina was reduced by 50% as LH levels rose significantly. By contrast, in females, this distance did not decrease until 6 days after ovariectomy, coincident with a delayed rise in LH levels. The percent area of each immunopositive terminal occupied by LHRH reaction product was smaller in intact males than females and increased after castration to reach a maximum 3 weeks after castration. By contrast, in females, the greatest percent area was observed in control diestrous females and decreased to a minimum 3 weeks after ovariectomy. Three weeks after gonadectomy, distance and area measurements no longer displayed significant sex differences. Transformations of LHRH terminals may be modulated by direct action on LHRH terminals or intervening neuronal or nonneuronal elements in the median eminence. Modulating factors may derive from local elements or circulating factors bound to local extracellular matrix.

Luteinizing hormone-releasing hormone terminals in the median eminence of rats undergo dramatic changes after gonadectomy, as revealed by electron microscopic image analysis.

Despite intense investigation, the modulation of LHRH release, essential to reproduction, is not fully defined. In this study we investigated whether dynamic transformations of individual LHRH terminals in the median eminence of the hypothalamus occurred as a function of gonadectomy in rats, using immunocytochemistry and electron microscopy with quantitative image analysis. One day after castration, the distance between LHRH terminals and the basal lamina was reduced by 50% as LH levels rose significantly. By contrast, in females, this distance did not decrease until 6 days after ovariectomy, coincident with a delayed rise in LH levels. The percent area of each immunopositive terminal occupied by LHRH reaction product was smaller in intact males than females and increased after castration to reach a maximum 3 weeks after castration. By contrast, in females, the greatest percent area was observed in control diestrous females and decreased to a minimum 3 weeks after ovariectomy. Three weeks after gonadectomy, distance and area measurements no longer displayed significant sex differences. Transformations of LHRH terminals may be modulated by direct action on LHRH terminals or intervening neuronal or nonneuronal elements in the median eminence. Modulating factors may derive from local elements or circulating factors bound to local extracellular matrix.

Luteolysis Is Linked to Luteinizing Hormone-Induced Depletion of Adenosine Triphosphatein Vivo*

An elevation of ATP levels in luteal cells markedly enhances their response to gonadotropin. In contrast, depletion of ATP in all cells leads to a series of interrelated events that produces irreversible cell injury. Since the corpus luteum has a transient existence, functional regression and involution of this gland play a fundamental role in the regulation of reproduction. The objective of the present studies was to evaluate whether the luteal ATP content may be regulated in an endocrine fashion and whether luteolysis may be linked to depletion of ATP in the corpus luteum in vivo. The present studies show that removal of the pituitary, maintenance of luteal function in hypophysectomized rats with PRL, or acute treatment with prostaglandin F2 alpha had no effect on luteal ATP levels. However, LH produced a rapid and marked decrease in adenine nucleotide levels in both intact and hypophysectomized PRL-replaced rats, whereas GTP levels were unaffected. In pituitary-intact rats, this same effect of LH occurred within 5 min, was maximal (40% depletion) within 30 min, and was sustained for many hours. Depletion of ATP by LH was dose dependent and evident with low doses of LH. In addition, a decrease in luteal ATP levels was seen during functional luteolysis in the rat, which was directly related to a rise in the serum levels of LH, but not FSH. In contrast, LH had no effect on ATP depletion in isolated cells prepared from the total luteinized ovary, or in enriched preparations of luteal cells. Thus, the depletion of ATP by LH in vivo appears to be mediated by intraovarian agents of unknown nature. We suggest that the rise in LH levels that follows functional luteolysis, due to reduced negative feedback by progesterone, produces a rapid decrease in luteal ATP levels which induces irreversible cell damage and, ultimately, involution of the corpus luteum. This effect would, presumably, be exacerbated as LH levels rise to maximum at ovulation or until LH receptors become down-regulated.

The role of the hypothalamic beta-adrenergic system in controlling the LH rise in short-term castrated rats.

Intraventricular infusions of adrenaline and various pharmacological agents acting on beta-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 microliter) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed beta 1- and beta 2-agonist), fenoterol (a beta 2-agonist) and atenolol (a beta 1-antagonist). In contrast, prenalterol (a beta 1-agonist) and (2RS,3RS)-3-isopropylamino-1-(7-methylindan-4-yloxy)++ +butan-2-ol (ICI 118,551) (a selective beta 2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective beta 2-agonist), propranolol (a mixed beta-antagonist) and metoprolol (a beta 1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118,551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118,551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a beta 2-stimulatory component and the suppression of a beta 1-inhibitory component.

Oestrous cycle-related LH responsiveness to naloxone: effect of high oestrogen levels on the activity of opioid receptors.

Endogenous opioid peptides have a tonic inhibitory control on LH secretion, participating in the functional changes of the hypothalamic-pituitary-ovarian axis. To evaluate the activity of the endogenous opioid systems during the oestrous cycle, we measured plasma LH levels after naloxone administration (5 mg/kg, s.c.) at 09.00 and 16.00 h on all days of the cycle (two further measurements were taken at 14.00 and 18.00 h on the day of pro-oestrus) and after one dose or one week's treatment with oestradiol benzoate (OB; 0.2 micrograms/rat). Concentrations of LH were measured in the same experimental models after injection of LH-releasing hormone (LHRH; 1 microgram/kg, i.p.) or saline. Naloxone induced a significant rise in LH levels on the day of oestrus, dioestrus day-1 and dioestrus day-2; this response was blunted on the morning of pro-oestrus and absent in the afternoon and after acute and chronic OB treatment. Conversely LHRH was most effective in increasing LH levels on the day of pro-oestrus and in OB-treated rats. These results indicate that opioid mechanisms, independently of the time of day and the pituitary responsiveness, exhibit a reduced activity when preovulatory changes occur, probably as a result of increased oestrogen levels.

Studies on the control of gonadotrophin release in the gonadectomized male rat: evidence for a lack of involvement of the hypothalamic noradrenergic system in the long-term castrated rat.

The effects of castration with or without testosterone replacement in the adult male rat were studied to investigate possible hypothalamic mechanisms by which changes in gonadotrophin secretion occur at different times after castration, with particular reference to the continuing LH rise and its lack of suppression by testosterone in the long-term castrated rat. Castrated rats received either subcutaneous silicone elastomer implants containing testosterone or empty implants at the time of castration, and a sham-operated group served as controls. At 1, 10 and 40 days after castration, there were six-, 15- and 25-fold rises respectively in LH and 1.5-, two- and fivefold rises in FSH. However, there were no significant changes in hypothalamic noradrenaline concentration and turnover or in alpha-adrenoceptor density and affinity at any time after castration. Testosterone implants were effective in suppressing gonadotrophin release at 1 and 10 days, but not at 40 days after castration, and did not significantly affect hypothalamic noradrenaline turnover or alpha-adrenoceptors at any time. Neither acute inhibition of the noradrenergic system, using either the alpha-adrenoceptor blockers phenoxybenzamine and phentolamine or the synthesis inhibitor alpha-methyl-p-tyrosine, nor chronic depletion of hypothalamic noradrenaline by 6-hydroxydopamine had any significant effect on the normal rise in LH levels seen on days 10 and 40 after castration, and did not alter the ability of testosterone to suppress LH levels. This indicates that, in the long-term castrated rat, the noradrenergic system may not be involved in the control of gonadotrophin release. However, at 16 h after castration, alpha-adrenoceptor blockers and alpha-methyl-p-tyrosine did reduce LH levels, indicating that the noradrenergic system is likely to be involved in the short-term response to castration.

Influence of pinealectomy on the suppression of gonadotropin secretion induced by hyperprolactinaemia in the adult male rat.

To investigate the role of the pineal gland in the long-term suppression of gonadotrophin secretion induced by prolactin, the effects of pinealectomy were studied in adult male rats with hyperprolactinaemia produced by the transplantation of two pituitary glands under the kidney capsule. Pinealectomy had no effect on basal levels of LH, FSH or prolactin. The presence of pituitary transplants induced a significant twofold increase in prolactin levels and a prolonged suppression in both LH and FSH. These changes were not affected by pinealectomy. Castration resulted in a similar rise in plasma levels of LH and FSH in rats with and without pituitary transplants. In control rats this rise in LH and FSH was reduced by testosterone-containing silicone elastomer implants (s.c) of 10 mm in length and delayed by implants of 30 mm. These rises in LH and FSH were significantly delayed (10-mm implant) or abolished (30-mm implant) in rats with pituitary transplants indicating an increase in sensitivity of the hypothalamic-pituitary axis to the negative feedback effects of testosterone in these animals compared to controls. These responses were not affected by pinealectomy. These results suggest that the pineal gland is not involved in the mechanism whereby pituitary grafts, possibly through their secretion of prolactin, cause long-term suppression of gonadotrophin secretion.

Effect of adrenalectomy or castration on the inhibition of gonadotrophin secretion induced by hyperprolactinaemia in the adult male rat.

To investigate the role of adrenal and gonadal steroids in the long-term suppression of gonadotrophin secretion induced by prolactin the effects of adrenalectomy or castration on the serum and pituitary levels of LH, FSH and prolactin and the hypothalamic content of LH releasing hormone (LH-RH) have been studied in adult male rats with hyperprolactinaemia produced by the transplantation of pituitary glands under the kidney capsule. Levels of LH and FSH in serum were significantly suppressed in al intact pituitary-grafted rats. Adrenalectomy on the day of pituitary implantation or 20 days later did not affect the suppression. However, castration on days 0, 28 or 49 after pituitary grafting resulted in a rise in levels of FSH in serum indistinguishable from that in control rats. While the rise in levels of LH after castration on day 0 was the same as the controls, this increase was significantly reduced 2 days after castration on days 28 and 49 after pituitary grafting. Castration resulted in an increase in the pituitary content of LH and a reduction in the hypothalamic content of LH-RH but no change in the pituitary content of FSH. Hyperprolactinaemia did not appear to affect these response. The present results showed clearly that the gonad but not the adrenal must be present for prolactin to exert an inhibitory effect on gonadotrophin secretion.

Effects of androgens, oestrogens and deoxycorticosterone acetate on plasma concentrations of luteinizing hormone in laying hens.

Testosterone, androstenedione, oestrone, oestradiol-17beta or deoxycorticosterone acetate (DOCA) were injected intramuscularly at several dose-levels and at various stages of the ovulatory cycle, and subsequent changes in plasma LH concentration were measured by radioimmunoassay. In 19 out of 24 hens, injection of 0.1, 0.5 or 1.0 mg DOCA/kg resulted in a mean maximal increase in plasma LH concentration of between 0.47 and 2.10 ng/ml. The magnitude of this response was not related to either the dose or the stage of the cycle at which the DOCA was injected. In the remaining five hens DOCA failed to stimulate LH secretion. Injection of either androstenedione, oestrone or oestradiol did not result in any increase in LH level in the circulation. In contrast, injection of 0.5, 1.0 or 2.0 mg testosterone/kg between 22 and 26 h after the terminal ovulation of a sequence resulted in mean maximal incremental changes in plasma LH level of 1.98 +/- 0.17, 2.17 +/- 0.21 and 2.41 +/- 0.31 (S.E.M.) ng/ml from pre-injection values of 1.38 +/- 0.16, 1.58 +/- 0.30 and 1.43 +/- 0.39 ng/ml (n=7, 6 and 5, respectively). The interval between the injection and the resulting rise in LH level was inversely proportional to the dose. The same doses of testosterone injected between 0 and 8 h after ovulation failed to stimulate LH secretion. There was also no significant increase in LH levels after injection of 0.5 and 1.0 mg testosterone/kg between 8 and 9 h after ovulation. However, injection of 2 mg testosterone/kg at this time resulted in a small but significant (P is less than 0.05) increase in LH levels. Since the largest ovarian follicle is more mature at 22-26 h after ovulation than at 0-9 h after ovulation, the ability of testosterone to cause the release of LH therefore appears to depend upon the degree of maturation of the ovarian follicle next due to ovulate.

Pituitary gonadotropin function during human pregnancy: serum FSH and LH levels before and after LHRH administration.

Pituitary gonadotropin reserve was evaluated in 8 normal pregnant women (13-35 weeks gestation) by measuring serum concentrations of FSH and LH (betaLH assay) before and after an IV bolus of 100 mug LHRH. Basal levels of FSH and LH were low or undetectable. LHRH administration failed to stimulate FSH release but did result in a small short-lived rise in LH levels. These findings provide further evidence that pituitary gonadotropin synthesis and release are inhibited during pregnancy.

Effect of intermittent infusion of LH-releasing hormone of serum LH and FSH levels in immature male rats.

The effect of intermittent intravenous infusions of LH-RH on serum LH and FSH levels was studied in immature male rats. At the end of the infusion, serum LH and FSH levels were higher than those after saline infusion. One hr after the end of infusion of LH-RH, serum LH levels fell, reaching saline control values, but FSH levels remained higher. Moreover, a pulsative pattern of LH release but not of FSH, was obtained during the intermittent infusion with LH-RH. These findings indicate that under appropriate conditions after administration of LH-RH, it is possible to find high GSH levels without a concomitant rise of LH levels. The continued elevation of FSH may be explained by the longer biological half-life of FSH. Estradiol benzoate depressed the basal serum GSH level and augmented the basal serum GSH level and augmented LH release after intermittent infusion with LH-RH, indicating that estrogen modified FSH/LH ratio. The results suggest that discordance of plasma LH and FSH levels which is occasionally observed in some physiological conditions does not necessarily indicate the presence of another FSH-RH which is distinct from LH-RH decapeptide.

The Control of Gonadotropin Secretion in Complete Testicular Feminization1

ABSTRACT Serum concentrations of LH, FSH, testosterone and estradiol were measured in 6 subjects with the complete form of testicular feminization who ranged in age from 0.5–21.0 yr. The 3 postpubertal subjects showed LH levels elevated above the age-matched eugonadal male range, while serum FSH, testosterone and estradiol levels were within normal male limits. The 3 prepubertal subjects showed normal or only slightly elevated LH and FSH concentrations. Serial LH, FSH and testosterone determinations over 1 month in the 21-yr-old subject showed no cyclic variation. Stilbestrol, but not fluoxymesterone, suppressed gonadotropinand testosterone levels in this subject. In 4 subjects, including the 0.5 yr old, castration resulted in a marked increment in FSH levels and a further rise in LH levels. Postcastration studies showed no gonadotropin suppression by dihydrotestosterone propionate, but significant suppression by testosterone propionate; similar effects were seen in 4 young adult castrate “controls”. Gona...

Periovulatory levels of plasma progesterone and luteinizing hormone in women.

ABSTRACT Plasma LH and progesterone levels were measured around the time of ovulation in 16 normal menstrual cycles. No increased levels of progesterone were found before the LH peak. The maximal LH peak levels lasted for 16–20 h at which time the plasma progesterone rose to a concentration of 1 to 2 ng/ml. Following the fall in the LH concentration, there was a rapid rise in the plasma progesterone concentration, indicating the formation of a corpus luteum. The lowest basal body temperature coincided with the first significant rise in LH levels.