Effect of luteinizing hormone releasing hormone pulse characteristics on comparative luteinizing hormone and follicle stimulating hormone secretion from superfused rat anterior pituitary cell cultures

We have shown that 4 ng luteinizing hormone releasing hormone (LHRH) pulses induced significantly greater luteinizing hormone (LH) release from proestrous rat superfused anterior pituitary cells with no cycle related differences in follicle stimulating hormone (FSH). Current studies gave 8 ng LHRH in various pulse regimens to study amplitude, duration and frequency effects on LH and FSH secretion from estrous 0800, proestrous 1500 and proestrous 1900 cells. Regimen 1 gave 8 ng LHRH as a single bolus once/h; regimen 2 divided the 8 ng into 3 equal 'minipulses' given at 4 min intervals to extend duration; regimen 3 gave the 3 'minipulses' at 10 min intervals, thereby further extending duration: regimen 4 was the same as regimen 2, except that the 3 'minipulses' were given at a pulse frequency of 2 h rather than 1 h. In experiment 1, all four regimens were employed at proestrus 1900. FSH was significantly elevated by all 8 ng regimens as compared to 4 ng pulses; further, 8 ng divided into 3 equal 'minipulses' separated by 4 min at 1 and 3 h frequencies (regimens 2 and 4) resulted in FSH secretion that was significantly greater than with either a single 8 ng bolus (regimen 1) or when the 'minipulses' were separated by 10 min (regimen 3). In experiment 2, at proestrus 1500, FSH response to the second pulse of regimen 4 was significantly greater than in regimen 2; LH release was significantly suppressed at pulse 2 compared to regimen 2 accentuating divergent FSH secretion. At estrus 0800, FSH response to the second pulse of regimen 4 was significantly stimulated FSH at proestrus 1900, 1500 and estrus 0800, FSH divergence was most marked at proestrus 1500. These data indicate a potential role for hypothalamic LHRH secretory pattern in inducing divergent gonadotropin secretion in the rat.     

The induction of divergent gonadotropin secretion in vitro by variations in luteinizing hormone releasing hormone pulse regimen

The effects of luteinizing hormone releasing hormone (LHRH) pulse amplitude, duration, and frequency on divergent gonadotropin secretion were examined using superfused anterior pituitary cells from selected stages of the rat estrous cycle. Cells were stimulated with one of five LHRH regimens. With low-amplitude LHRH pulses (regimen 1) in the presence of potentially estrogenic phenol red, LH response in pituitary cells from proestrus 1900, estrus 0800, and diestrus 1,0800 were all significantly larger (P less than 0.05) than the other stages tested. In the absence of phenol red, responsiveness at proestrus 1900 was significantly larger than proestrus 0800, proestrus 1500, and estrus 0800 (P less than 0.01, 0.05, and 0.05, respectively); other cycle stages tested were smaller. No significant differences were observed between cycle stages for follicle-stimulating hormone (FSH) secretion in the presence or absence of phenol red. Because pituitary cells at proestrus 1900 were the most responsive to low-amplitude 4 ng LHRH pulses, they were also used to study the effects of LHRH pulses of increased amplitude or duration and decreased frequency. Increasing the amplitude (regimen 2) or the duration (regimens 3 to 5) increased FSH secretion; this effect was greatest with regimens 3 and 5. When regimens 3 and 5 were studied in pituitary cells obtained at proestrus 1500, FSH was significantly increased by both regimes, but most by regimen 5; furthermore, LH release was significantly reduced. When regimens 3 and 5 were studied in pituitary cells obtained at estrus 0800, FSH release was elevated most significantly by regimen 5. Thus, variations in LHRH pulse regimen were found to be capable of inducing significant divergence in FSH release from superfused anterior pituitary cells derived from specific stages of the estrous cycle.     

Effect of alterations in pulsatile luteinizing hormone release on ovarian follicular atresia and steroid secretion on diestrus 1 in the rat estrous cycle

This study examined the importance of pulsatile luteinizing hormone (LH) release on diestrus 1 (D1; metestrus) in the rat estrous cycle to ovarian follicular development and estradiol (E2) secretion. Single injections of a luteinizing hormone-releasing hormone (LHRH) antagonist given at -7.5 h prior to the onset of a 3-h blood sampling period on D1 reduced mean blood LH levels by decreasing LH pulse amplitude, while frequency was not altered. Sequential injections at -7.5 and -3.5 h completely eliminated pulsatile LH secretion. Neither treatment altered the total number of follicles/ovary greater than 150 mu in diameter, the number of follicles in any size group between 150 and 551 mu, or plasma E2, progesterone, or follicle-stimulating hormone (FSH) levels. However, both treatments with LHRH antagonist significantly increased the percentage of atretic follicles in the ovary. These data indicate that: 1) pulsatile LH release is an important factor in determining the rate at which follicles undergo atresia on D1; 2) reductions in LH pulse amplitude alone are sufficient to increase the rate of follicular atresia on D1; 3) an absence of pulsatile LH release for a period of up to 10 h on D1 is not sufficient to produce a decline in ovarian E2 secretion, most likely because the atretic process was in its early stages and had not yet affected a sufficient number of E2-secreting granulosa cells to reduce the follicle's capacity to secrete E2; and 4) suppression or elimination of pulsatile LH release on D1 is not associated with diminished FSH secretion.     

Hypersecretion of follicle-stimulating hormone (FSH) on estrous afternoon in rats treated with RU486 in proestrus

Summary 1. Intact or ovariectomized (OVX) cyclic rats injected or not with RU486 (4 mg/0.2 ml oil) from proestrus onwards were bled at 0800 and 1800h on proestrus, estrus and metestrus. Additional RU486-treated rats were injected with: LHRH antagonist (LHRHa), estradiol benzoate (EB) or bovine follicular fluid (bFF) and sacrified at 1800 h in estrous afternoon. LH and FSH serum levels were determined by RIA.2. RU486-treated intact or OVX rats had decreased preovulatory surges of LH and FSH, abolished secondary secretion of FSH and hypersecretion of FSH in estrous afternoon. The latter was decreased by LHRHa and abolished by EB or bFF. In contrast, EB induced an hypersecretion of LH in RU486-treated rats at 1800h in estrus.3. It can be concluded that in the absence of the proestrous progesterone actions, the absence of the inhibitory effect of the ovary in estrus evoked a LHRH independent secretion of FSH.     

Splenic macrophages enhance prolactin and luteinizing hormone action in rat luteal cell cultures.

We have reported that splenic macrophages play a role in the regulation of progestin secretion in rats. In this study, splenic macrophages were obtained from cycling rats at different estrous cycle stages and co-cultured with luteal cells from mid-pseudopregnant rats in the absence/presence of prolactin (PRL) or luteinizing hormone (LH). The effect of macrophages on the luteotropic action of PRL and LH was evaluated with 2 parameters, i.e. an increase in total progestin output (progesterone plus 20 alpha-hydroxyprgn-4-en-one [20 alpha-OHP]), and an increase in the progesterone to 20 alpha-OHP (P/20 alpha-OHP) secretion ratio. Splenic macrophages obtained from proestrous or metestrous rats enhanced the PRL action to increase the P/20 alpha-OHP secretion ratio, but those from estrous or diestrous donors did not. Only macrophages from proestrous donors enhanced the PRL action to increase the total progestin output. In contrast, the LH action increasing the P/20 alpha-OHP secretion ratio was enhanced by splenic macrophages regardless of the donors' estrous cycle stages. The LH action increasing the total progestin output was enhanced only by proestrous or metestrous macrophages. Therefore, if luteal cells are co-cultured with proestrous macrophages, the luteotropic actions of PRL and LH can be fully expressed. These results indicate that splenic macrophages directly act on luteal cells and enhance the luteotropic action of PRL and LH, and that this function of splenic macrophages is modified somehow according to the donors' estrous cycle stages.     

Acute and chronic effects of the fornix section on cyclic gonadotropin secretion and ovulation in the rat.

The fornix was sectioned in the frontal plane by means of a razor blade knife, and acute and chronic effects of this section on gonadotropin secretion were estimated. The 5-day cyclic rat which received the section of fornix under either anesthesia at 12:00 on the day of diestrus II showed advancement of the proestrous and estrous vaginal smears and as well as ovulatory gonadotropin release by one day. It was revealed that the primary effect was the inducement of FSH release on the day of section. The 4-day cyclic rat bearing the fornix section chronically resumed vaginal cyclicity after elapsing the diestrous period for 18 to 25 days. The rat ovulated normally and mean number of ova inoviducts was not different from that in the intact rat. However, the sectioned rat hadan higher concentrations of pituitary and serum FSH on the day of diestrus II than thatin the intact rat, and had an higher concentration of serum LH on the day of estrus. These results indicate that the hippocampus exerts the inhibitory influence on LH and FSH release and if this is eliminated the facilitatory influence dominates the brain mechanism controlling gonadotropin release, resulting in the advancement of estrous cycle (the acute effect) or the increase of gonadotropin release (the chronic effect).     

Mechanism of the stimulatory action of antisteroid RU486 on follicle-stimulating hormone secretion in the cyclic Rat

These experiments explored the mechanism underlying FSH hypersecretion on estrous afternoon in rats injected with RU486 (RU) on proestrus. Four-day cyclic rats were injected with RU at 12:00 h on proestrus (1 or 4 mg/0.2 ml oil; s.c.), and its effects on LH and FSH secretion at 18:30 h on estrus were compared with those of antiprogestagens ZK299 (ZK) (1 or 4 mg/0.2 ml oil; s.c.) and Org31806 (OR) (2 or 8 mg/0.2 ml oil; s.c.). Additionally, rats treated with RU or nembutal (PB) (60 mg/kg; i.p. at 13:00 h on proestrus) were injected with an LHRH antagonist (LHRHa) at 10:00 h on estrus (1 mg/0.2 ml saline; s.c.) or progesterone (P) (7.7, 15.5 or 30.9 mg/0.2 ml oil; s.c.) on proestrus at 10:00 h in RU-injected rats and at 14:00 h in PB-injected rats. Animals were killed by decapitation at 18:30 h on estrus and serum LH and FSH concentrations were determined. Rats treated with 1 or 4 mg of RU or Org or 4 mg of ZK recorded increased serum FSH on estrous afternoon, while 1 mg ZK had no effect. PB increased mainly serum LH levels and, to a lesser extent, FSH levels. P decreased serum FSH concentrations in both RU- and PB-injected rats. LHRHa reversed the effects of PB on FSH secretions, but reduced FSH hypersecretion induced by RU only. These results are interpreted to mean that, in the absence of proestrous afternoon P-inhibitory action of the neural stimulus controlling LHRH release, FSH secretion on estrous afternoon involves two components: one is LHRH dependent while, in contrast to LH secretion, the other is LHRH independent, and only expressed in a low estrogen background.     

Adrenergic mechanisms in the control of myometrial activity in mice. Changes on estrous cycle

Correlation between contractile activity and norepinephrine (NE) release induced by electrical stimulation or by high K+ depolarization has been analyzed in isolated preparations of mouse uterus throughout the different stages of the estrous cycle. Both the contractile activity induced by electrical stimulation and the capacity to maintain contracture, after changing the physiological bathing solution by high K+ solution, followed the same pattern: estrous greater than proestrous greater than diestrous greater than metestrous. High-K+ induced 3H-NE release was also different according to the stage of the estrous cycle. 3H-NE release was significantly less in estrous than in diestrous uterine horns. EC50 values for inhibiting contractile response, for isoprenaline, norepinephrine and phenylephrine were significantly greater in metestrous than in other stages of the estrous cycle. On the other hand, reserpinized mouse uteri showed an increase in EC50 values in the stages tested. The data support the hypothesis that in a mouse uterus, sex steroid hormones could affect beta-adrenergic receptor function indirectly, perhaps through an action on adrenergic neurons by a mechanism affecting NE release from sympathetic terminals.     

Alterations in the proestrous pattern of median eminence LHRH, serum LH, FSH, estradiol and progesterone concentrations in middle-aged rats

The purpose of the following study was to assess the changes in the proestrous hormone profile in middle-aged cycling rats to better understand the inter-relationship and possible interaction of these hormones during the transition to estrous acyclicity. Median eminence LHRH concentrations and serum LH, FSH, estradiol and progesterone concentrations were measured in young (3-4 months old) and middle-aged (8-10 months old) proestrous rats at 0900, 1200, 1500 and 1800h. The data demonstrate that (1) baseline hormone concentrations prior to the surge at 0900h are the same in middle-aged and young rats; (2) the proestrous gonadotropin surge is temporally delayed in middle-aged rats; (3) this delay is preceded by lower median eminence LHRH concentrations and serum estradiol concentrations at 1200h; (4) serum progesterone concentrations are lower in middle-aged rats during the preovulatory gonadotropin surge (at 1500 and 1800h) probably as a consequence of the delayed LH surge.     

Melanin-concentrating hormone stimulates the release of luteinizing hormone-releasing hormone and gonadotropins in the female rat acting at both median eminence and pituitary levels

The purpose of this study was to investigate whether melanin-concentrating hormone (MCH) acts directly on the median eminence and on the anterior pituitary of female rats regulating LHRH and gonadotropin release. In addition, immunohistochemistry was used to examine the density and distribution of MCH-immunoreactive fibers in the median eminence of proestrous rats. MCH-immunoreactive fibers were found in both the internal and external layers of the median eminence and in close association with hypophysial portal vessels. In the first series of in vitro experiments, median eminences and anterior pituitaries were incubated in Krebs-Ringer bicarbonate buffer containing two MCH concentrations (10(-10) and 10(-8) M). The lowest MCH concentration (10(-10) M) increased (P < 0.01) LHRH release only from proestrous median eminences. Anterior pituitaries incubated with both MCH concentrations also showed that 10(-10) M MCH increased gonadotropin release only from proestrous pituitaries. In the second series of experiments, median eminences and pituitaries from proestrous rats were incubated with graded concentrations of MCH. MCH (10(-10) and 10(-9) M) increased (P < 0.01) LHRH release from the median eminence, and only 10(-10) M MCH increased (P < 0.01) LH and FSH release from the anterior pituitary. The effect of MCH on the stimulation of both gonadotropins from proestrous pituitaries was similar to the effect produced by LHRH. Simultaneous incubation of pituitaries with MCH and LHRH did not modify LH but increased the FSH release induced by LHRH. The present results suggest that MCH could be involved in the regulation of preovulatory gonadotropin secretion.     

Polycystic ovarian condition in estradiol valerate-treated rats: spontaneous changes in characteristic endocrine features

A chronic anovulatory polycystic ovarian (PCO) condition can be induced in rats with estradiol valerate (EV). We have previously shown that the early stages (8-10 wk after EV treatment) of the condition are characterized by low basal plasma luteinizing hormone (LH) and estradiol concentrations, as well as poor LH responsiveness to LH-releasing hormone (LHRH). These observations suggested that alterations in pituitary LH secretory activity may be involved in induction and maintenance of the PCO condition. In order to examine this possibility we have measured basal plasma LH and follicle-stimulating hormone (FSH) concentrations at various times (6, 15, 20 and 22 wk) after treatment with EV. AT 22 wk animals were subjected to a double LHRH pulse or equivalent treatment with saline. Basal plasma LH concentrations in EV-treated animals doubled between 6 and 22 wk. Despite this sharp increase, basal plasma LH concentrations at 22 wk were still significantly lower in EV-treated animals compared to proestrous controls. Basal FSH in EV-treated animals, remained in the proestrous range throughout the 22-wk period. Pituitary FSH and LH secretions in response to the LHRH challenge were significantly greater in EV-treated animals compared to proestrous controls. Plasma estradiol was significantly greater at 22 wk post-EV treatment than at 9 wk and this difference was reflected in the histology of the endometrium. These results indicate that a PCO condition is compatible with radical alterations in basal LH, and responsiveness to LHRH. Thus, aberrations in the ability to secrete LH do not appear to be causal in maintaining the condition.     

Effect of PACAP on LH release studied by cell immunoblot assay depends on the gender, on the time of day and in female rats on the day of the estrous cycle

We have previously demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) can be released from cultured rat anterior pituitary cells and when added to the medium in physiological concentration it releases LH from individual gonadotropes. In the present work, we studied whether the release of PACAP and the responsiveness of LH cells to PACAP depend on the gender, on the time of day when the animals were sacrificed, and in females on the stage of the estrous cycle. Anterior pituitary cells were cultured on nitrocellulose membrane. We found that the number of PACAP releasing cells was higher in proestrous than in diestrous female or in male rats and their number was always higher in the evening than at the other times. The effect of PACAP on LH cells was stimulatory in the morning of proestrus and diestrus. In proestrous rats, PACAP did not influence LH release in the afternoon or the evening, but in diestrous rats it decreased it in the afternoon and the evening. In males, there was a decrease of LH due to PACAP treatment at 10 and 20 h; however, PACAP did not influence LH at 16 h. It was concluded that in vivo PACAP might be involved in the circadian and episodic release of LH at pituitary level.     

Changes in the dynamics of luteinizing hormone-releasing hormone-stimulated secretion of luteinizing hormone during sexual maturation of female rats

Our aim was to identify age-related changes in the dynamics of luteinizing hormone (LH) release that may contribute to the decline in pituitary sensitivity to luteinizing hormone-releasing hormone (LHRH) during sexual maturation of female rats. We studied LHRH-stimulated LH secretion curves of superfused pituitaries from rats ranging in age from 10 days to the first estrous cycle. Pituitary fragments were exposed for 10 min to medium alone or to medium plus LHRH; incubation continued in medium alone for 130 min and effluent was collected for LH analysis. Secretion curves were compared on the basis of total secretion (area under the curve), maximal change in LH secretion rate, and rates of rise and decay of the curves. The data show that total LH secretion in response to LHRH is greatest in 15-, 20-day-old and first-proestrus animals. Also, the maximal change in LH secretion rate was greater, and the increase in LH secretion rate faster in younger animals than in 30-day-old animals. Analysis of secretory granules in LH-containing gonadotropes of 15- and 30-day-old animals revealed changes in he granule population with age. We conclude that younger animals respond faster with a greater LH secretion response to LHRH than do 30-day-old or first-estrus animals, and that these age-related changes in the dynamics of LH secretion may be due in part to maturation of the LH secretory granules.     

Detrimental effects of short-term ethanol exposure on reproductive function in the female rat

To more completely assess the means by which alcohol impairs the female reproductive cycle in rats, we have measured hypothalamic luteinizing hormone-releasing hormone (LHRH), pituitary LHRH receptor content, and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), and progesterone (P). After two successive cycles, the animals began receiving either an alcohol or a isocaloric control liquid diet regimen beginning on the first day of diestrus, with continued monitoring of the estrous cycle throughout the experiment. An additional set of controls consisted of animals maintained on lab chow and water provided ad libitum. Our results indicate that those animals receiving the control diets showed uninterrupted estrous patterns, whereas those animals receiving the alcohol diet remained in diestrus. Additionally, the alcohol-treated animals showed an increase (p less than 0.05) in LHRH content, with a concomitant decrease (p less than 0.01) in serum LH, and an increase (p less than 0.01) in serum Prl. No significant differences were detected in serum FSH levels or pituitary LHRH receptor content. No differences were detected in serum P levels. These results indicate that short-term alcohol administration disrupts the female reproductive cycle, causing persistent diestrus, and support our hypothesis that the alcohol-induced depression in serum LH levels is due to a diminished release rate of hypothalamic LHRH.     

Passive immunization of the pig against gonadotropin releasing hormone during the follicular phase of the estrous cycle

Three experiments were conducted to determine the effects of passively immunizing pigs against gonadotropin releasing hormone (GnRH) during the follicular phase of the estrous cycle. In Experiment 1, sows were given GnRH antibodies at weaning and they lacked estrogen secretion during the five days immediately after weaning and had delayed returns to estrus. In Experiment 2, gilts passively immunized against GnRH on Day 16 or 17 of the estrous cycle (Day 0 = first day of estrus) had lower (P<0.03) concentrations of estradiol-17beta than control gilts, and they did not exhibited estrus at the expected time (Days 18 to 22). When observed three weeks after passive immunization, control gilts had corpora lutea present on their ovaries, whereas GnRH-immunized gilts had follicles and no corpora lutea. The amount of GnRH antiserum given did not alter (P<0.05) serum concentrations of LH or pulsatile release of LH in sows and gilts. In Experiment 3, prepuberal gilts were given 1,000 IU PMSG at 0 h and GnRH antiserum at 72 and 120 h. This treatment lowered the preovulatory surge of LH and FSH, but it did not alter serum estradiol-17beta concentrations, the proportion of pigs exhibiting estrus, or the ovulation rate. These results indicate that passive immunization of pigs against GnRH before initiation of or during the early part of the follicular phase of the estrous cycle retards follicular development, whereas administration of GnRH antibodies during the latter stages of follicular development does not have an affect. Since the concentration of antibodies was not high enough to alter basal or pulsatile LH secretion, the mechanism of action of the GnRH antiserum may involve a direct ovarian action.     

Effects of complete hypothalamic deafferentation on the estrous phase of follicle-stimulating hormone release in the cyclic rat

We investigated whether neural afferents to the medial basal hypothalamus play an acute role in the estrous phase of FSH release in the 4-day cyclic rat. A cannula was inserted into the right atrium of the heart under brief ether anesthesia during the early afternoon of proestrus for subsequent blood collections and injection of LHRH. In some of the rats, the medial basal hypothalamus was surgically isolated from the rest of the brain with a small knife under brief ether anesthesia between 2000 h and 2130 h of proestrus. Control groups consisted of naive rats which were not treated during the night of proestrus and sham-operated animals in which the knife was lowered to the corpus callosum between 2000 h and 2130 h or proestrus. Rats were bled at 2200 h of proestrus and at 0200 h, 0600 h and 1000 h of estrus for radioimmunoassay of plasma FSH and LH. The plasma FSH levels in all 3 groups between 2200 h of proestrus and 1000 h of estrus were elevated above levels observed in other cannulated rats bled to the onset of the proestrous phase of FSH release at 1400 h of proestrus. There were no statistically significant differences in plasma FSH or LH concentrations at any of the time periods between the 3 groups of serially bled rats. The deafferentation procedure did not appear to impair the pituitary gland's ability to secret gonadotrophins as injection of 50 ng of LHRH after the bleeding at 1000 h of estrus caused substantial elevations in plasma FSH and LH concentrations which were not different between the 3 groups. The results suggest that neural afferents to the medial basal hypothalamus play no acute role in the estrous phase of FSH release in the cyclic rat.     

Superfused pituitary cell cultures: effects of culture conditions on apparent responsiveness to LHRH stimulation administered as short duration pulses

We wished to study estrous cycle related differences in LH and FSH responsiveness to pulsatile LHRH. Such studies are very difficult to perform in vivo under controlled conditions; therefore, an in vitro superfused anterior pituitary cell culture system was evaluated for its capacity to support differences in estrous stage associated LHRH responsiveness. Three vital culture system parameters were evaluated; these parameters were (1) culture medium composition, (2) duration allowed for cell attachment to microcarrier beads and (3) superfusion flow rate utilized during pulsatile LHRH stimulation. It was found that a culture system which utilized 10% Nu Serum in DMEM (final protein concentration of 1.8 mg/ml; final serum concentration of 2.5%), an attachment time of 48 hrs and a flow rate of 0.125 ml/min most successfully maximized LH responsiveness at the lowest serum concentration. These studies indicated that although one may be able to observe LHRH responsiveness under a wide range of culture conditions, responsiveness may nonetheless be maximized by judicious adjustment of culture conditions.     

Gonadotropin-releasing hormone in third ventricular cerebrospinal fluid of the heifer during the estrous cycle

The release profile of GnRH in cerebrospinal fluid (CSF) and its correlation with LH in peripheral blood of ovary-intact heifers during the estrous cycle were investigated. A silicon catheter was placed into the third ventricle of six heifers using ultrasonography. During the mid-luteal phase, the heifers were injected with prostaglandin F(2alpha) to induce luteolysis. Surges of CSF GnRH (66.7 h after prostaglandin F(2alpha) administration) and peripheral LH (66.3 h) occurred simultaneously and were coincident with the onset of estrus (67.0 h). Duration of elevated GnRH concentration considerably overlapped with the estrous phase in each of the heifers. Mean pulse frequencies of both GnRH and LH were significantly higher during the proestrous and early luteal phases than during the mid-luteal phase, while mean concentration and pulse amplitude of both GnRH and LH were not different between these three phases. Of all the GnRH pulses identified, more than 80% were accompanied by an LH pulse during the proestrous and early luteal phases. However, the proportion of GnRH pulses that were coincident with an LH pulse during the mid-luteal phase decreased to 60%. The results clearly demonstrate that a dynamic (pulse) and longer-term (surge) changes of GnRH release into CSF are physiologically expressed during the estrous cycle in heifers, and the pattern of pulsatile GnRH secretion in heifers depends upon their estrous cycle.     

Short-term pulsatile administration of luteinizing hormone releasing hormone in male adolescents with multiple idiopathic pituitary hormone deficiencies

In order to define both level and severity of defect in patients with idiopathic multiple pituitary hormone deficiencies (MPHD) and to find out which patient might benefit from pulsatile LHRH substitution therapy, the effect of short-term pulsatile LHRH infusion in 6 affected male adolescents was studied. Controls were 9 boys with constitutional delay of puberty (CD). During a spontaneous nocturnal plasma profile LH and FSH levels were prepubertal with little evidence of pulsatile secretory LH activity in all MPHD patients. During short-term pulsatile LHRH stimulation (36 h), however, all showed a significant rise in mean LH and FSH levels (p less than 0.0001). Linear regression analysis revealed significant continuous increases of FSH (p less than 0.001) in all patients and of LH (p less than 0.01) in all but one patient. These changes were not accompanied by an increase of testosterone, androstenedione and DHAS levels. Since all MPHD patients showed steadily increasing gonadotropin levels if stimulated in a pulsatile manner, we conclude that the defect might only in part be located at the pituitary level. Long-term pulsatile substitution therapy with LHRH is likely to be successful in these patients as has been demonstrated in patients with known hypothalamic defect.