LH Stores Research Articles

Changes in pituitary LH content and LH secretion in the long-term ovariectomized rat during prolonged infusion of LRH.

LH secretion and the depletion of the pituitary LH stores caused by continuous infusion of LRH, were studied in the 5-weeks ovariectomized rat. After 1 day of infusion at the rate of 416 ng/h, pituitary LH content decreased to about 40% of its initial value. Upon continuation of the infusion the LH content increased slowly until, after 7 days, it increased to about 54% of the original value. The plasma LH concentrations, after having reached peak values of 7122 +/- 291 ng/ml after 2 h of infusion, declined to a plateau at about 300 ng/ml but it took 5 days to reach this value. When after either 2 or 8 days of LRH infusion at the rate of 416 ng/h the infusion was changed to a 'supramaximal' rate of 10,400 ng/h for 24 h, a transient secondary rise of LH secretion was induced. The magnitude of the secondary response, was essentially the same after 2 or 8 days of LRH infusion, but these secondary responses were significantly smaller than the LH-response during a similar LRH-infusion in previously untreated ovariectomized rats.

TSH Release during the Estrous Cycle of the Rat: Variations in Responsiveness to Cervicovaginal Stimulation

Serum TSH, LH and FSH were measured at various times during the day, during the estrous cycle of the rat. Proestrous surges of FSH and LH were detected as previously reported. TSH values fell to low levels in the late afternoon on each day of the cycle. There was a significant elevation of TSH at 13.00 h on both proestrus and estrus. The elevation of TSH on proestrus was accompanied by a significant fall in pituitary TSH stores. LH stores were also significantly depleted by 19.00 h on proestrus. Cervicovaginal stimulation by a glass rod provoked a significant rise in serum TSH 3 h after stimulation at 10.00 h on estrus but not on other days of the cycle. Responsiveness to a test dose of TRH varied during the cycle. It was maximal on proestrus and declined to minimum values on diestrus day II. Values were further lowered after ovariectomy but were restored to diestrus day II levels by treatment with estradiol. It is concluded that there are important cyclic variations in TSH release in the female rat, that cervicovaginal stimulation can provoke TSH release on estrus and that these changes are associated with altered responsiveness to TRH. We conclude that ovarian steroids modulate the release of TSH from the pituitary and affect the responsiveness to cervicovaginal stimulation. These changes are presumably brought about by alterations in TRH release and in responsiveness of the pituitary to the neurohormone.

Effects of morphine and naloxone on phasic release of luteinizing hormone and follicle-stimulating hormone.

SummaryIn ovariectomized rats given estradiol benzoate (EB), followed 3 days later by EB or progesterone, morphine, and naloxone altered the LH and FSH surges on the day of treatment (Day 1) and on the next day (Day 2). In the EB-EB-treated rats, morphine prevented, whereas naloxone enhanced the surge of LH and FSH on Day 1. On Day 2, the morphine-treated rats showed a large rebound surge of LH and FSH, whereas the naloxone-treated rats showed no surge. In the EB-progesterone-treated rats, morphine blocked, whereas naloxone had no effect on the LH and FSH surge on Day 1. On Day 2, the morphine-treated rats showed a large LH and FSH surge, whereas the naloxonetreated rats showed no surge. The effects of these drugs on the Day 2 surge of LH and FSH were found not to be the result of a build up or depletion of releasable stores of LH in the pituitary on Day 1. These results suggest a possible role for the endogenous opioid peptides in modulating steroid regulation of the neural surge signal for LH and FSH.

TIME-DEPENDENT DECREASE OF PITUITARY RESPONSE TO LH-RH AFTER CHRONIC TREATMENT OF INTACT FEMALE RATS WITH ETHINYLOESTRADIOL AND NORETHINDRONE

ABSTRACT The effect of daily injections of 50 μg ethinyloestradiol and 1 mg norethindrone upon basal and LH-RH-stimulated LH release was investigated in intact adult female rats during a period of 30 days. Basal plasma LH was depressed by about 30 % during the whole time of steroid treatment, and returned to the level of the control values two weeks after discontinuation. The injection of 30 ng and 150 ng LH-RH into untreated rats resulted in a significant increase of plasma LH which was, however, not dose-dependent. After the treatment with ethinyloestradiol and norethindrone for 5 days, the pituitary response to 150 ng was approximately four times higher than that to 30 ng. The LH release after injection of 150 ng LH-RH decreased significantly with the duration of steroid treatment, and was totally abolished by 30 days; whereas two weeks after the termination of steroid application the pituitary responded to LH-RH in the same manner as in control rats. When 30 ng LH-RH were injected into oestrogen/norethindrone treated rats, no decrease in LH release was found until day 20 of the experiment. By 30 days of treatment no rise in plasma LH could be elicited. The activity of the LH-RH-degrading enzyme L-cystine arylamidase was stimulated during the treatment with ethinyloestradiol and norethindrone in the pituitary by approximately 100 %, whereas almost no effect on this enzyme was seen in the hypothalamus. It is concluded that the chronic treatment of intact female rats with ethinyloestradiol and norethindrone causes time-dependent and reversible alterations in the storage of LH in the pituitary. The elevated activity of the LH-RH-degrading enzyme in the pituitary is possibly involved in these processes and/or in the mechanism responsible for the depression of basal LH.

Effects of estradiol-17beta on the induction of gonadotropin release by electrical stimulation of the hypothalamus in rhesus monkeys.

Serum LH and FSH were measured at 60, 30, and 0 min before, at 5, 15, and 30 min during, and at 10, 45, and 90 min after bilateral electrical stimulation (ES) of various hypothalamic regions in 12 unanesthetized ovariectomized rhesus monkeys. ES of the arcuate-ventromedial nuclei (medial basal hypothalamus; MBH) induced a prompt increase in serum LH that persisted throughout stimulation and returned to basal levels within 90 min thereafter. FSH was also released, but the release was slower and less dramatic than that of LH. Sham stimulation (0muA) caused no change in serum gonadotropins. The amount of LH released after MBH-ES depended upon current strength (1.0 mA greater than 0,5 or 0.7 mA). Three sequential 30-min MBH-ES trials at 90-min intervals induced comparable LH responses and 3 h of continuous MBH-ES maintained elevated serum LH levels throughout the stimulation period, suggesting that these stimulation period, suggesting that these stimulation parameters did not completely deplete pituitary stores of releasable LH. The character of the LH response was similar in individual monkeys through 3 to 24 trials during 4 to 18 months. Comparisons were made of the effects of estradiol-17beta (E2) treatment at different doses and for different intervals of time before MBH-ES. ES-induced LH release was not affected by low levels (25 and 55 pg/ml) ofE2 for 48 h, but was reduced by higher E2 concentrations (100 or 230 pg/ml). E2 concentrations of 100 pg/ml had no effect at 24 h, but reduced MBH-ES-activated LH release at 48 to 96 h; the degree of depression was time-related (48 h less than 72 h less than 96 h). ES of the preoptic-suprachiasmatic region (rostral hypothalamus; RH) in non-E2-treated monkeys also released LH, but this increase was less than after MBH-ES. FSH release was not measurable after RH-ES. In contrast to the depressed LH response to MBH-ES after 48 h of E2 (100 pg/ml), the response to RH-ES was not inhibited by this E2 regimen. These data suggest that ES of an area extending caudally from the rostral hypothalamus to the arcurate-median eminence region will evoke LH release in rhesus monkeys. This electrically induced gonadotropin release was affected by administration of physiological levels of E2 but the nature of effect depended on the specific region stimulated: distinct inhibition of the gonadotropic response to MBH-ES and slight facilitation of the response to RH-ES.

The apparent paradox of the negative and positive feedback control system on gonadotropin secretion

The separate and interactive effects of estradiol (E2) and luteinizing hormone-releasing factor (LRF) on the dynamics of LH storage and release were studied. Measurements were made of the serum gonadotropin responses to submaximal doses of LRF, given as brief pulses or infused over an extended period to normal women at various stages of the follicular phase of their menstrual cycles and to hypogonadal women with and without estrogen treatment. The two-pool concept of pituitary gonadotropin was verified; the dynamic responses of the two pools to the inputs of LRF and E2 were investigated and related to pituitary properties of sensitivity and reserve. Our results indicate that LRF appears to serve as a primary drive on the gonadotrophs, stimulating gonadotropin synthesis and storage (second pool), as well as release (first). E2 for the most part, amplifies the action of LRF except that it impedes LRF-induced release of gonadotropin. E2 augments the second pool activity (reserve) preferentially, and the relative activity of the first pool appears to be influenced by the E2-dependent self-priming effect of LRF. The interactions of the various elements of the system, when combined, provide a U-shaped curve to describe the over-all capacity of the gonadotrophs as a function of a broad range of E2 inputs. Negative and positive feedback of E2 are revealed to operate by different mechanisms and to represent different segments of a single U-shaped curve rather than paradoxically disparate actions.

Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropins in hypophysogonadal disorders of children and adolescents: VII. Constitutional delay of puberty in males

Serum gonadotropins (LH and FSH) were measured by radioimmunoassay before and after intravenous injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone in 20 male patients, aged 15 to 18 years, with constitutional delay of puberty. Basal plasma levels of LH and FSH were in the prepubertal range. After administration of LH-RH, the increase in LH was significantly high than in prepubertal control subjects, aged 1 to 13 years; the difference between test patients and pubertal control subjects was not significant. The increase in FSH was in the prepubertal range, significantly lower than that in pubertal control subjects. This discrepancy between LH and FSH responses to LH-RH is similar to that observed in normal boys at the late prepubertal stage and suggests that an elevation of readily releasable pituitary stores of LH correlates with the first step of pubertal onset in males, even if puberty is delayed.

Induction of LH surges by continuous infusion of LH-RH1.

Preovulatory LH surges were measured in cannulated proestrous rats. Such LH peaks were also obtained by infusing pentobarbital-blocked animals with LH-RH for periods of up to 20 h; this suggested that the pituitary LH stores were exhausted. However, the total amount of LH secreted appeared more or less determined by the LH-RH dose, indicating that the size of the releasable LH pool is not fixed.

Interactions of prostaglandin E 1 (PGE 1) and LRH on anterior pituitary function

Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE 1), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the in vitro release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all in vitro experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE 1 in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE 1 had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulated prolactin release in the absence of LRH. Prostynoic acid stimulated LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.

The effect of the pineal gland on ovulation and pregnancy in the rat.

The possibility of the involvement of the pineal in ovulation and pregnancy was examined in the rat. Pinealectomized, sham-operated, melatonin-injected, and saline-injected rats were killed on Day 1, 8, 16, 22, or 23 (day of delivery) and ovulation rates, ovarian, anterior pituitary, and uterine weights, pituitary LH and FSH content, and serum LH concentration were compared among the four treatment groups. No difference was noted either in the time of ovulation or in the number of ova released among the four treatment groups. Also, no difference was noted in the number of pups or fetuses, number of implantation sites, or number of reabsorbed fetuses. The organ weights in pinealectomized rats were generally higher and the organ weights in melatonin-injected rats were generally lower than their respective controls only on Day 1 and the day of delivery, i.e., on the days when the animal is not, in fact, pregnant. The rise in pituitary LH content in all four treatment groups during pregnancy with no concomitant change in serum LH indicates that the rise in pituitary LH during pregnancy may represent only an increased storage of LH by the pituitary with little or no LH release. A possible explanation for the increased serum LH concentration on Days 1 and 23 in melatonin-injected animals is offered. A fourfold increase in pituitary FSH is noted by Day 16 in all four groups. The pituitary content of FSH remained high until Day 22 and fell by the day of delivery to a level equal to that on Day 1. It appears, therefore, that under “normal” laboratory conditions the role that the pineal gland plays in ovulation and pregnancy is minimal at best. The greatest effect of the pineal on the parameters measured appears to occur on Days 1 and 23, i.e., before fertilization and after delivery.

Progesterone: sites of action in inhibiting ovulation in hamsters.

A single subcutaneous injection of progesterone (0.5 mg/animal at 17.00 hours) on Day 3 of the cycle (Day 1 = day of vaginal discharge) interfered with ovulation and external vaginal discharge in all the animals. Lower doses were only partly active. Intravenous administration of LH, FSH or their combination at 14.00 hours on Day 4 failed to restore ovulation in such animals, implying a direct action of the administered progesterone on the ovary. A large dose of oestradiol benzoate (400 mug/animal) also proved inactive suggesting that progesterone did not interfere with ovulation solely through antioestrogenic action. Depletion of the pituitary LH stores normally found in association with ovulation and ovulatory peak of LH in plasma seen in control animals were not observed in the progesterone-treated hamsters suggesting a further action of progesterone at the pituitary-hypothalamic level in inhibiting ovulation. Administration of synthetic LRF (100 ng/animal, i.v.) on Day 4 to hamsters treated with progesterone caused an increase in plasma LH 15 min later which was comparable to the rise observed in control animals given a similar injection of LH-RF, implying lack of action of progesterone at the pituitary level. It is concluded that progesterone acts centrally, principally on the hypothalamus, and peripherally on the ovary to interfere with ovulation in hamsters. It is possible that the anovulatory state accompanying pregnancy results from these actions.

Interactions of prostaglandin E 1 (PGE 1) and LRH on anterior pituitary function

Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE1), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the in vitro release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all in vitro experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE1 in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE1 had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulated prolactin release in the absence of LRH. Prostynoic acid stimulated LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.

A model for LH levels in the recently-castrated adult rat and its comparison with experiment

A mathematical model for LH levels in the recently-castrated rat is presented. It is simply based on an increase of both production and release of pituitary LH after castration. Solutions of the model equations are shown to correlate well with data in the adult rat when the release rate-constant is taken as β = 0·4 ± 0·15 day−1 and the production-increase rate-constant is taken as γ = 0·07 ± 0·03 μg (LH)/mg (pit.)/day2. The available data do not permit any sex difference to be determined in these two rate-constants. The correlation also does not depend sensitively on variations in their numerical values. A minimum LH storage level in the pituitary, LHp0, is an integral postulate of the model; a value of 0·25 μg/mg being estimated from data in the normal estrous cycle. With this model for post-castration behavior, the greater initial increase of serum LH in the male than in the female can be explained as primarily due to the larger pituitary LH concentration in the male at the time of castration. Since the analysis makes no attempt to relate post-castration behavior to events in the estrous cycle, the female at proestrous is excluded from consideration. When analyzing serum LH data measured in ng(LH)/ml (serum) it is important to note the difference in LH distribution volume between males and females of different body weights. The ratio of pituitary weight to distribution volume is shown to be an important scaling factor for correlating serum hormone data.

Participation of the amygdala and of the cerebellum in the feedback effects of progesterone.

Bilateral implantation of small amounts of progesterone in the amygdala, cerebellum, and median eminence of castrated female rats results in an increase of pituitary stores of LH and in a decrease of hypothalamic stores of LH-RF. Similar implants placed subcutaneously or in the cerebral cortex are ineffective. It is suggested that the amygdala and the cerebellum contain receptors sensitive to progesterone and intervene in modulating the negative, inhibitory effect that this steroid exerts onLH secretion.

Effects of estrogen and-or progesterone on serum and pituitary gonadotropin levels in ovariectomized rats.

Pituitary concentration and total content of LH, FSH and prolactin as well as serum levels of the hormones were measured in rats ovariectomized for 4–6 weeks and either untreated or primed with estrogen, progesterone, or both, 72 hr prior to decapitation. Estrogen stimulated synthesis and release of prolactin whereas progesterone did not alter these processes. Estrogen alone or in combination with progesterone caused increased pituitary stores of LH, perhaps by reducing endogenous LH-RH. Either steroid, administered alone or in combination with the other, increased the pituitary content of FSH, and FSH release was only partially inhibited by estrogen or estrogen and progesterone.

Some observations on the gonadotrophin inhibiting and anti-progestational properties of 20 -dihydroprogesterone.

ABSTRACT 20α-dihydroprogesterone (20α-OH-P) was administered for 10 days either alone (2 or 4 mg/rat, sc) to explore its biological properties or in combination with progesterone (2 or 4 mg/rat, sc) to test its potential as an antiprogestin. When administered alone to intact rats the hydroxylated steroid, unlike progesterone, failed to disturb the oestrous cycle, cause ovarian or uterine atrophy, mucify the vagina or significantly modify pituitary stores of LH or FSH. In unilaterally spayed rats, 20α-OH-P proved ineffective in decreasing ovarian compensatory hypertrophy. Thus the loss of progestational properties in 20α-OH-P was associated with diminution in gonadotrophin-inhibiting properties. When administered to animals primed with oestrogen, 20α-OH-P exerted either an additive or synergistic effect on the trauma-induced deciduomata in bilaterally spayed rats and on the progestational proliferation in the immature rabbit. 20α-OH-P by itself had no significant effect under these conditions. In no instance did the hydroxylated steroid antagonize the effects of progesterone. In the pregnant rats bilaterally spayed and maintained on suboptimal doses of progesterone (1 mg/rat/day), simultaneous administration of 20α-OH-P (2 mg/day) did not antagonize the pregnancy supporting effect of progesterone. Thus under the conditions of these experiments 20α-OH-P failed to manifest any antiprogestin potential. It appears that 20α-OH-P may play a physiological role by potentiating or augmenting the effect of progesterone on decidualization.

Levels of LH in the sera and pituitaries of female lambs following ovariectomy and administration of estrogen.

The concentration of LH in sera and pituitaries was determined by radioimmunoassay in 21 female lambs after ovariectomy and/ or administration of estradiol 17β (E2). At 5- days-of-age lambs were divided to form four groups. Lambs of Group C were controls, Group 0 were ovariectomized, Group E were implanted subcutaneously with E2 and Group OE were ovariectomized and given E2. The lambs were bled daily by venipuncture for 25 days after birth and then on alternate days until 44 days when they were killed. The LH in the serum of lambs in Group C and 0 began to increase to a level detectable by the assay when the lambs were 12 days of age. LH in the serum of Group C increased to 2-4 ng/ml when the lambs were 21–24– days-of-age but did not rise thereafter. Lambs of Group 0 had a sharp rise in LH in the serum beginning at day 12 which continued to day 44. The rise in LH in the serum of individual lambs of both Group C and 0 was not continuous from day to day as there were numerous cases of declining levels from one day to the next. The LH in serum of lambs in Groups E and OE, receiving 15-20 μg of exogenous E2 daily, remained below that of the sensitivity of the assay. The concentration of LH in the pituitaries of Group C was significantly greater (P < 0.001) than in groups 0, E and OE. The uteri in lambs of Group C were significantly heavier than those of Group O (P < 0.05), but were significantly lighter than those of Groups E and OE (P < 0.005). On the basis of this evidence we conclude that the ovarian-pituitary feedback system is functioning in lambs within a few days after birth, and that sufficient ovarian steroids are being synthesized and released to affect uterine growth but not to suppress release of LH. The rate of release of LH from the pituitary of the ovariectomized lamb is approximately equal to that of synthesis, hence there is little storage of LH. Administration of 15-20 μg of exogenous E2 daily, suppresses both synthesis and release of pituitary LH and increases uterine weight. (Endocrinology90: 981, 1972)

Pituitary LH content during delayed implantation induced by different treatments in rats.

ABSTRACT The capacity of oestrogens to induce nidation during delayed implantation and the known dependence of oestrogen secretion on LH prompted a detailed study of the pituitary LH content of rats in which implantation of blastocysts was delayed by various procedures. Implantation was delayed by Provera (2 mg), reserpine (200 μg), oral dosing with the antioestrogen I.C.I. 46,474 (40 μg) or clomiphene (100 μg), ovariectomy followed by progesterone treatment and finally by permitting mothers mated postpartum to suckle a large litter (10 pups). The pituitary LH stores (OAAD method) of such animals were compared with those of rats killed in prooestrus and oestrus and on day 9 of pseudopregnancy, pregnancy or lactation. Hypophyseal LH levels were very low during delayed implantation induced by Provera or suckling and very high during that induced by ovariectomy followed by progesterone treatment compared with those in prooestrous, pseudopregnant or pregnant controls. By contrast, no significant change in LH stores was observed when nidation was delayed by single injections of I.C.I. 46,474 or clomiphene. Delayed implantation could not be induced in intact rats with chlormadinone or norgestrel even when given in large doses (2–8 mg/day). It is postulated that to delay implantation in the presence of the ovaries, a centrally acting agent must be capable of decreasing synthesis of LH in the pituitary.

Effects of prostaglandin F2-alpha on pituitary luteinizing hormone content of pregnant rats: a possible explanation for the luteolytic effect.

Summary. Prostaglandin F2α induced degeneration of embryos in intact pregnant rats but not in ovariectomized rats maintained on progesterone. The pituitary lh stores in the intact, treated rats were significantly higher than those in the pregnant, pseudopregnant or cyclic controls. The prostaglandin failed to inhibit the ovulatory release of lh in the cyclic rat. It is suggested that the luteolytic effect of PGF2α may be mediated in part by the increased synthesis and secretion of lh.

Analysis of initial and delayed effects of orchidectomy and ovariectomy on pituitary and serum LH levels in adult and immature rats.

The initial LH secretory responses to castration were examined in adult and immature rats of both sexes, using an 0:0 radioimmunoassay for rat LH. The patterns of response differed markedly between males and females. Adult males exhibited a dramatic increase in serum LH levels, which was detectable by 8 hr after gonadectomy, and reached a plateau at about 20 times pre-castration levels by 18 hr. This plateau was sustained through the fourth day; serum LH levels then increased about 4-fold further over the next month. The initial response in females was less marked and no plateau phase was evident. Although serum LH levels did not match those of comparable males during the first 10 post-castration days, they did reach or surpass them later. The pattern of pituitary LH changes also differed: in males, LH stores initially fell, reaching a nadir at about day 4; females exhibited no such fall. This sex difference in the pattern of the initial LH secretory responses to castration was evident in prepubertal castrates as well, although immature males did not respond as markedly as adult males. The weaker initial response of the female was evident in rats castrated at various times during the estrus cycle. Serum LH appeared to rise more rapidly in rats ovariectomized during diestrus than in rats spayed at other times, but no female castrate ever exhibited the very marked initial serum LH increment characteristic of the adult male. Analysis of concomitant changes in serum and pituitary LH levels suggest that LH net synthesis increased quite soon after castration, perhaps even as early as LH release (i.e., within the first 8–18 hr after gonadectomy). However, it should be emphasized that studies such as these may not accurately define the time lags in the responses of the LH secretory system to removal of steroid negative feedback signals, since surgical gonadectomy may itself influence the LH secretory response(s). (Endocrinology86: 1102, 1970)