Increase In Pulsatile LH Secretion Research Articles

Do cyclic female goats respond to males with an increase in LH secretion during the breeding season?

The male effect is currently only used during seasonal or lactational anoestrus because the response is thought to be blocked in cyclic females by periods of elevated progesterone. In this study, we tested whether cyclic, female goats would respond to male exposure with an increase in pulsatile LH secretion. During May (breeding season; Southern Hemisphere) the cycles of 16 Australian Cashmere goats were synchronised using intravaginal progesterone pessaries. Pessary insertion was staggered to produce groups in their early luteal (EL; n = 8) and late luteal phases (LL; n = 8). The LL group was retrospectively subdivided into mid-luteal (ML; n = 4) and late luteal (LL; n = 4) groups due to differences in oestrous cycle length that emerged during the study. Male exposure stimulated an increase in LH pulse frequency in the EL and LL groups ( P < 0.01) but not in the ML group ( P > 0.1). This increase was accompanied by an increase in basal and mean concentrations of LH in the LL group ( P < 0.05) but not in EL ( P < 0.1) or ML ( P > 0.1) group. There was no effect of male exposure on LH pulse amplitude ( P > 0.1). Progesterone concentrations differed among all groups on the day of male exposure ( P < 0.05) and declined significantly over the 12-h sampling period in the LL group ( P < 0.05). Prolactin concentrations declined in the EL group but did not change significantly in the ML or LL group. In conclusion, male exposure induced an increase in pulsatile LH in goats in the early and late luteal phases of the oestrous cycle. The high concentrations of progesterone in females in the mid-luteal phase appeared to block the male effect.

The introduction of rams induces an increase in pulsatile LH secretion in cyclic ewes during the breeding season

Application of the ram effect during the breeding season has been previously disregarded because the ewe reproductive axis is powerfully inhibited by luteal phase progesterone concentrations. However, anovulatory ewes treated with exogenous progestagens respond to ram introduction with an increase in LH concentrations. We therefore tested whether cyclic ewes would respond to ram introduction with an increase in pulsatile LH secretion at all stages of the estrous cycle. We did two experiments using genotypes native to temperate or Mediterranean regions. In Experiment 1 (UK), 12 randomly cycling, North of England Mule ewes were introduced to rams midway through a frequent blood-sampling regime. Ewes in the early (EL; n = 6) and late luteal (LL; n = 6) phase responded to ram introduction with an increase in LH pulse frequency and mean and basal concentrations of LH (at least P < 0.05). In Experiment 2 (Australia), the cycles of 32 Merino ewes were synchronised using intravaginal progestagen pessaries. Pessary insertion was staggered to produce eight ewes at each stage of the estrous cycle: follicular (F), early luteal (EL), mid-luteal (ML) and late luteal (LL). In all stages of the cycle, ewes responded to ram introduction with an increase in LH pulse frequency ( P < 0.01); EL, ML and LL ewes also had an increase in mean LH concentration ( P < 0.05). In conclusion, ram introduction to cyclic ewes stimulated an increase in pulsatile LH secretion, independent of ewe genotype or stage of the estrous cycle.

Bicuculline Infusions Advance the Timing of Luteinizing Hormone Surge in Proestrous Rats: Comparisons with Naloxone Effects

The role of GABA neurons in the control of the surge of LH secretion was investigated by examining whether GABA^ receptor antagonist bicuculline (BIC) infusion prior to the LH surge could advance the timing of the proestrous surge in the rat. The effect of the opioid receptor antagonist naloxone (NAL) was also examined for comparison. Female rats in proestrus were iv infused with NAL (2 or 5 mg/hr) or BIC (50 mg/kg/hr) for a 3-hr (1000-1300 hr) period during which blood samples were collected at 6-min intervals through an intraatrial cannula in freely moving rats. The animals that received infusion were bled again over a 7-hr period (1400-2000 hr) at l-hr intervals. NAL infusions at 2 mg/hr induced an increase in pulsatile LH secretion, but did not affect the timing, magnitude, and duration of the LH surge. NAL infusions at 5 mg/hr not only induced a greater increase in pulsatile LH secretion but also resulted in a pronounced LH surge prematurely. In contrast, during BIC infusion, no significant changes in LH secretion were seen until 1200 hr, but afterward a rapid and sharp rise in LH secretion occurred, suggesting the premature LH surge. These results are consistent with the hypothesis that the tonic LH secretion is sensitive to NAL, but not to BIC, whereas the surge of LH secretion is sensitive to barbiturates that have been known as the activator of GABAA receptor complex. Therefore, we suggest that there is a LHRH surge generator, distinct from the pulse generator, in the brain, and it has GABA neurons in its circuitry.

Age-related changes in biogenic amines, opiate, and steroid receptors in the prepubertal bull calf.

Events leading to the increase in pulsatile LH secretion during prepubertal development in the bull calf may include removal of inhibitory or the development of stimulatory mechanisms affecting the hypothalamic release of GnRH. To examine possible contributing systems, serial blood samples were collected from Holstein bull calves at 2, 5, and 10 wk of age one day prior to receiving either no treatment (controls) or two injections of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of catecholamine synthesis. Blood was sampled every 10 min for 5 h and serum was analyzed for LH by RIA. Following treatment, animals were killed and hypothalamic and pituitary tissues were removed for analysis of total opiate receptors, mu-opiate receptors, estrogen and androgen receptors and concentrations of monoamines: dopamine, the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DO-PAC), norepinephrine, serotonin, and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA). Pulses of LH increased from non-detectable at 2 wk to nearly 1.5 pulses per sampling period at 10 wk. Pulse height rose to 0.95 +/- 0.16 ng/ml at 10 wk. Total opiate receptor number as determined by binding to naloxone was unchanged in all tissues between 2 and 10 wk. In contrast, mu-opiate receptors (DAGO binding) increased 2-fold in the preoptic-anterior hypothalamic area between 5 and 10 wk. No age-related changes in estrogen receptor concentrations were observed in any tissue except the anterior pituitary in which binding increased 3.2-fold between 2 and 10 wk. A similar increase was not noted for androgen receptors in the pituitary; however, testosterone binding in the preoptic-anterior hypothalamic area was 4.6-fold higher at 5 wk compared to levels at 2 and 10 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Acute, Intracerebroventricular Administration of Insulin on Serum Concentrations of Luteinizing Hormone, Insulin, and Glucose in Ovariectomized Lambs during Restricted and Ad Libitum Feed Intake1

To test the hypothesis that the increase in pulsatile LH secretion associated with increased feed intake in growth-restricted lambs is due to elevated insulin concentrations, we evaluated the effects of intracerebroventricular (ICV) administration of insulin on patterns of LH in ovariectomized ewe lambs. After weaning (10 wk of age), 12 lambs were fed to maintain a mean body weight of 18.3 kg. At approximately 32 wk of age a permanent cannula was inserted into the lateral ventricle of each lamb. For the first experiment, animals received 3 ICV injections of either 500 ng (n = 6) or 500 micrograms (n = 6) insulin. Blood samples were collected every 10 min for 8 h, with animals receiving injections at 2, 4, and 6 h. Patterns of LH during the 2-h preinjection period were compared to those in the subsequent 2-h periods following each insulin injection. Insulin did not affect mean LH, LH pulse frequency, or LH pulse amplitude. Only the 500-micrograms injections increased (p < 0.0001) peripheral insulin and decreased (p < 0.001) peripheral glucose. The experimental protocol was repeated during a second experiment conducted after 2 wk of ad libitum feeding, when animals weighed an average of 21.4 kg. Increased feed intake was associated with increases in mean LH, LH pulse frequency, and insulin (p < 0.05). Both doses of insulin decreased (p < 0.01) mean LH and LH pulse frequency. The 500-micrograms injections increased (p < 0.0001) peripheral insulin and decreased (p < 0.001) glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nutrition and season on the onset of puberty in the beef heifer.

Age at puberty is a major determinant of lifetime reproductive efficiency of beef cows. Research conducted during the past 20 yr has documented the major endocrine events leading to first ovulation in heifers. The critical event seems to be a prepubertal increase in pulsatile LH secretion. Environment influences timing of puberty onset in beef heifers. Nutrition and season are two of the better-defined variables that have been studied. Age at puberty is related inversely to plane of nutrition. The effect of nutrition on sexual maturation involves effects on timing of the prepubertal increase in LH secretion and seems to involve the LH pulse generating system located in the hypothalamus. The precise mechanism by which nutrition influences pulsatile LH secretion has not been elucidated, but signals reflecting metabolic status seem to be involved. Seasonal conditions of the early (birth to 6 mo of age) and late (6 to 12 mo of age) postnatal periods also influence timing of puberty onset in the heifer. Autumn-born heifers attain puberty at younger ages than do spring-born heifers, and exposure to spring-summer temperatures and photoperiods during the second 6 mo of life reduces age at puberty regardless of season of birth. Photoperiod may be the major seasonal cue that influences puberty onset in cattle. Limited evidence suggests that melatonin, a pineal hormone, is involved with transducing photic stimuli into neuroendocrine signals that influence LH secretion. If the physiological mechanisms mediating the effects of nutrition and season on timing of puberty onset are determined, then management strategies for reducing age at puberty can be enhanced.

Influence of glucose infusions on luteinizing hormone secretion in the energy-restricted, primiparous, lactating sow

The objective of this experiment was to evaluate the influence of glucose infusion during lactation on LH secretion in the energy-restricted sow. Ten primiparous Landrace x Yorkshire sows (152 kg postfarrowing) were fed a low-energy (6.5 Mcal of ME/d), high-lysine (45 g/d), corn-soybean meal diet throughout lactation. On d 18 of lactation, sows received a continuous infusion (1 L/12 h) of glucose (50% dextrose solution) or .9% saline from 1200 to 2400. Blood samples were drawn every 15 min for an 18-h period on d 18 to evaluate concentrations of plasma glucose, serum insulin, and serum LH before (600 to 1200) and during (1215 to 2400) the infusions. The glucose infusion immediately increased (P less than .001) plasma glucose and serum insulin relative to preinfusion levels. Glucose and insulin concentrations in sows receiving the glucose infusion were higher (P less than .001) throughout the infusion period relative to concentrations in sows receiving a saline infusion. Glucose infusions had no influence on LH pulsatility during the 12-h infusion period. In contrast to the response observed in the nutrient-restricted gilt, these results indicate that glucose infusions do not result in an immediate increase in pulsatile LH secretion in the energy-restricted, lactating sow.

Effects of bovine follicular fluid on the secretion of LH and FSH in inhibin-immunized seasonally anoestrous ewes

It has been shown previously that treatment of seasonally anoestrous ewes with steroid-free bovine follicular fluid (FF), a crude inhibin-containing preparation, leads to a decrease in plasma FSH level which is accompanied by a marked increase in pulsatile LH secretion. Since FF contains several factors (e.g. activin, follistatin, unidentified components) other than inhibin, which might act to modify gonadotrophin secretion, it was of interest to establish whether these concurrent effects of FF on FSH and LH secretion persisted in ewes which had been actively immunized against a synthetic peptide replica of the alpha subunit of bovine inhibin. In June 1989 (anoestrous period) groups of inhibin-immune and control ewes (n = 5 per group) received 6-hourly s.c. injections of either bovine serum (2 ml) or one of two doses of FF (0.5 ml or 2 ml) for 3 days. Blood was withdrawn at 6-h intervals for 6 days beginning 24 h before the first injection. On the final day of treatment, additional blood samples were withdrawn at 15-min intervals for 8 h to monitor pulsatile LH secretion. Ewes were then challenged with exogenous gonadotrophin-releasing hormone (GnRH; 2 micrograms i.v. bolus) to assess pituitary responsiveness. In control ewes, FF promoted a dose-dependent suppression of basal (maximum suppression 65%; P less than 0.01) and post-GnRH (maximum suppression 72%; P less than 0.01) levels of FSH in plasma. This was accompanied by an increase (P less than 0.01) in LH pulse frequency from 1.40 +/- 0.24 (S.E.M.) to 3.20 +/- 0.37 pulses/8 h. In contrast, FF did not affect secretion of either FSH or LH in inhibin-immunized ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of Pulsatile Luteinizing Hormone and Testosterone Secretion during Short Term Food Restriction in the Adult Male Rhesus Monkey (Macaca mulatta)*

To determine whether signals occurring during the early stages of undernutrition can have a suppressive effect on the central drive to the reproductive axis, the effects of 1 day of fasting on pulsatile LH and testosterone secretion were examined in adult male rhesus monkeys. Monkeys were maintained with chronic indwelling venous catheters on tether/swivel systems. One day of fasting caused a small weight loss of 0.1-0.2 kg, which represented a loss of 1-3% of the initial body weight. On a day of normal feeding monkeys showed a mean of 4.57 +/- 0.53 LH pulses/12 h (measured from 1900-0700 h). On a subsequent day of fasting LH pulse frequency was significantly reduced to 1.86 +/- 0.46 pulses/12 h (P less than or equal to 0.05). Likewise, there was a similar decrease in testosterone pulse frequency on a day of fasting. The substantial decrease in LH/testosterone pulse frequency was not caused by the intensive blood-sampling regimen, in that collection of blood samples for 12 h on 2 consecutive days of normal feeding did not result in a decrease in either LH or testosterone pulse frequency. Administration of exogenous GnRH in doses of 0.05-0.3 microgram/kg caused LH pulses of similar magnitudes on a day of normal feeding and a day of fasting, suggesting that the decrease in LH pulse frequency during the day of fasting reflects a decrease in GnRH stimulation of the pituitary rather than a loss of pituitary sensitivity to GnRH. Measurement of pulsatile LH across 3 consecutive days (e.g. a day of normal feeding, a day of fasting, and a day of refeeding) indicated that LH pulse frequency is slow before the time that the meal is missed on the second day and remains low throughout the day of fasting (normal feeding, 7 +/- 1.16 pulses/24 h; fasting, 3.33 +/- 0.33 pulses/24 h). Refeeding a normal meal at 1100 h on the third day resulted in an immediate and sustained increase in pulsatile LH secretion above normal frequency (11.07 +/- 0.33 pulses/24 h). These results indicate that very brief periods of undernutrition can significantly suppress the central drive to the reproductive axis in male rhesus monkeys, and this suppression can be rapidly reversed by refeeding. These findings argue against the hypothesis that undernutrition only suppresses central drive to the reproductive axis once a substantial amount of body weight has been lost.

Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16.3 +/- 2.7 (S.E.M.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1-5) and clinical progress followed for a mean duration of 22.4 +/- 8.5 months during which 33 hormone profiles were obtained. Nocturnal (23.00-09.00 h) LH pulse frequency increased to a peak of 0.54 +/- 0.03/h at stage 2 which was followed by a gradual decline to 0.42 +/- 0.04/h at stage 5. The appearance of LH pulses in the evening (20.00-23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0.53 +/- 0.08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH:FSH ratio reversed from less than 1 to greater than 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20.42 +/- 11.57 at stage 1 to 35.96 +/- 20.83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.

Endogenous opioid regulation of pulsatile luteinizing hormone secretion during sexual maturation in the female sheep.

The developing female sheep, which attains puberty after 25 weeks of age, was used as an experimental model to investigate the role of endogenous opioid peptides in the control of pulsatile LH secretion during sexual maturation. Treatment of ovary-intact prepubertal sheep at 12 weeks of age with the opiate antagonist naloxone resulted in a dose-dependent increase in LH secretion. Subsequent studies used ovariectomized (OVX) lambs implanted with capsules containing 17 beta-estradiol to provide a constant, ovarian steroid feedback signal throughout development. Naloxone treatment (hourly iv injections of 1 mg/kg BW for 4 h) produced an increase in the frequency of episodic LH secretion at all prepubertal ages, when lambs were highly sensitive to the estradiol negative feedback. However, increases in LH pulse frequency were also induced by naloxone treatment at a postpubertal age in estradiol-treated OVX sheep, indicating that opioid inhibition is still present at a time when sensitivity to the feedback effects of ovarian steroids is markedly reduced and endogenous LH secretion is increased. These observations in ovary-intact and estradiol-treated OVX lambs suggest that opioid mechanisms inhibit pulsatile tonic LH secretion during both the prepubertal and postpubertal periods. Endogenous opioid inhibition of LH secretion is not dependent on the presence of ovarian steroids, as evidenced by the response to naloxone 3 weeks after removal of an estradiol implant from OVX lambs, when LH pulse frequency was already high. Naloxone treatment increased LH pulse frequency further, at both a prepubertal age (18 weeks) and a postpubertal age (38 weeks). Naloxone also increased LH pulse frequency in OVX lambs in which LH secretion was inhibited chronically by progesterone rather than by estradiol. The response to naloxone was similar in postpubertal P-treated OVX lambs and age-matched prepubertal P-treated OVX controls in which puberty had been delayed by means of an inhibitory seasonal photoperiod. In addition, after removal of steroid implants to allow LH secretion to increase, the degree of inhibition of LH secretion by the opiate agonist morphine was similar between age-matched postpubertal sheep and those with photoperiodically delayed puberty. We conclude that endogenous opioid mechanisms are an important inhibitory mechanism controlling pulsatile LH secretion in the developing sheep. However, changes in opioid inhibition are unlikely to underlie the decrease in sensitivity to steroid negative feedback and increase in pulsatile LH secretion that occur at puberty.