Control Of Luteinizing Hormone Secretion Research Articles

Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep.

The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40-60 min) and had elevated LH levels (16.1 +/- 1.6 ng/ml; mean +/- SE) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

Pharmacological studies on the noradrenergic control of luteinizing hormone secretion in the domestic fowl

A neuropharmacological approach was utilized in order to investigate catecholaminergic involvement in the control of LH secretion in the domestic fowl. Inhibition of catecholamine synthesis by α-methyl- p-tyrosine (αMpt) at several doses was accompanied by significant reductions in the circulating LH concentration of 6-week-old male cockerels. Plasma LH was similarly depressed following the selective inhibition of NE synthesis by either diethyldithiocarbamate (DDC) or FLA 63. Blockade of α 1-adrenergic receptors with phenoxybenzamine was consistently associated with precipitous declines in plasma LH concentrations. Stimulation of α-adrenergic receptors by phenylephrine and clonidine elevated circulating LH levels. Activation of the dopaminergic system by apomorphine depressed LH release. However, pimozide was without effect. These data suggest that norepinephrine is involved in the stimulation of LH release, while dopamine may exert an inhibitory influence. Evidence of some stimulatory β-adrenergic effect is also described.

Aminergic involvement in the control of luteinizing hormone secretion in the domestic fowl

Neuropharmacologic agents have been used, in vivo, to investigate the possible involvement of the biogenic amines in the hypothalamic control of luteinizing hormone (LH) secretion in the domestic fowl. Inhibitors of norepinephrine (NE)/dopamine (DA) synthesis (for DA NE α-methyl- p-tyrosine, α-mpt; for NE diethyldithiocarbamic acid, DDC) and granule reuptake of catecholamines (reserpine) and the α-adrenergic antagonist (phenoxybenzamine) induced reductions in the circulating concentrations of LH. The administration of p-chlorophenylalanine (an inhibitor of 5-hydroxytryptamine (5HT) synthesis) and methysergide (a 5HT antagonist) also depressed plasma levels of LH. Neither β-adrenergic (propranolol) nor cholinergic (atropine) blockers affected circulating LH levels. These data suggest the involvement of a catecholamine (probably acting via α-adrenergic receptors), together with some serotoninergic components in the hypothalamic control of LH in the chicken.

A Priming Effect of Luteinizing Hormone Releasing Hormone on Bovine Pituitary Cells In Vitro

The capacity of pituitary glands to release luteinizing hormone (LH) in response to LH-releasing hormone (LHRH) in vivo may be increased by previous frequent exposures to small quantities of LHRH. This phenomenon, called LHRH self-priming, may play an important role in the control of LH secretion. Our initial objective was to determine whether LHRH self-priming occurs via a direct effect on bovine pituitary cells. Subsequently, we studied the effects of interval between LHRH exposures and source of pituitary glands (steers versus cows) on LHRH self-priming. Cells from bovine anterior pituitary glands were dispersed and mixed with Sephadex-G25, and the mixture was poured into glass columns. Columns were superfused and effluent medium was assayed for LH. Challenges were .1 ng LHRH/ml or 0 ng LHRH/ml (sham) each for 10 minutes. In one experiment, quantity of LH released by a second exposure to LHRH averaged 124 ± 6 ng/ml, which was greater than that released in response to an LHRH challenge (90 ± 4) given 40 min earlier. In a second experiment, variables were LHRH sequence (sham-LHRH versus LHRH-LHRH) and interval between challenges (40, 80, 160 and 320 min). Quantities of LH released in response to LHRH following the sham challenge or the first of two LHRH challenges were not different. However, LH released by a second LHRH challenge was 48, 39 and 48% greater (P<.01) than that released by the first when the interval between challenges was 40, 80 and 160 min, respectively. But when the interval was 320 min, no LHRH self-priming occurred. In a third experiment, variables were LHRH sequence (sham-LHRH versus LHRH-LHRH) and sex of the pituitary gland donor (cows versus steers). Interval between challenges was 50 minutes. Quantity of LH released after the second LHRH challenge was 50% greater (P<.01) than that released after the first LHRH challenge when cells were from pituitary glands of cows. Self-priming did not occur when cells were from pituitary glands of steers. However, this experiment compared a pool of pituitary cells from steers with one from cows, so there was no estimate of individual animal variation. Thus, our data do not prove that this difference exists but merely raises that possibility. We conclude that LHRH can self-prime bovine pituitary cells and that the degree to which priming occurs may be dependent upon the interval between exposures to LHRH.

Beta-Endorphin alters luteinizing hormone secretion via the amygdala but not the hypothalamus.

Morphine and enkephalins are able to alter pituitary hormone secretion. It has been postulated that they do not act directly at the pituitary, but rather that the hypothalamus is the site at which inhibition or stimulation of pituitary hormone secretion is initiated. On the other hand, endogenous opiates have been located in distinctly different neuronal regions, including areas outside the hypothalamus. The effects of beta-endorphin on plasma luteinizing hormone (LH) levels have not been explored, and the present experiments attempt to elucidate the contribution and the possible site of action of beta-endorphin in the control of LH secretion. The results show that beta-endorphin inhibits pituitary LH secretion if applied into the amygdala but not when given into the hypothalamus.

Luteinizing hormone secretion and female lordosis behavior in male pigs.

Serum concentrations of luteinizing hormone (LH) and testosterone were monitored during the first 9 weeks of life in male pigs. In boars, testosterone was constant during this period, and LH was elevated from birth through day 21 and declined between days 21 and 28 to levels observed in adult boars. Castration on day 3 reduced testosterone concentrations without having an immediate effect on LH, but after day 21, LH was consistently greater in castrated males than in boars. Responsiveness of the early postnatal testes to LH was shown by reduced testosterone concentrations after treatment with LH-antiserum on day 2. Norethindrone had no effect on LH or testosterone when given on day 2 but decreased the concentrations of these hormones in 5-month-old boars. Similarly, estrogen had no effect on LH secretion in 4-day-old boars. In 9-month-old castrated males, estrogen decreased LH concentrations during the first 48 h of daily treatment, but after this, LH increased and returned to pretreatment levels by 88 h. Also, daily estrogen treatment of castrated males induced female lordosis behavior. From these observations we conclude that negative feedback control of LH secretion is inoperative in neonatal male pigs and that exogenous estrogen can induce responses characteristic of females in castrated postpubertal males.

Sexual differentiation and feedback control of luteinizing hormone secretion in the rhesus monkey.

The inhibitory and stimulatory effects of estradiol-1 7i3 (E2) on systemic Iuteinizing hormone (LH) levels were studied in three groups of gonadectomized rhesus monkeys: 7 females (F), 7 males (M), and 7 androgenized females (AF). The AF animals, androgenized by exposure to exogenous testosterone in utero, showed masculinization of the external genitalia and behavior after ‘birth. All animals were compared for the short-term inhibitory effects (�74 h) of E2 on LH concentrations. Concentrations of 70 to 100 pg/mI of E5, achieved by sc implantation of a silastic E2-filled capsule, caused a 40 percent decline in serum concentrations of LH at 6 h; but no significant differences in LH concentrations were found between experimental groups at 6, 24, 48 or 74 h after E2 treatment. The long-term negative feedback effects of E2 were studied in 2 trials. In trial 1, at 1 week (but not at 2 or 3 weeks) F treated with small amounts of E2 (approximately 48 pg/mI, N = 45) had significantly less serum LH compared to preimplant levels (P<0.05) than M treated similarly. In trial 2, the effects of various doses of E2 (0.5, 1.5 and 3.0 cm silastic implants) on LH secretion in F, M and AF animals were studied. The 0.5 cm implant of E2, which sustained a blood level of approximately 22 pg/mI, significantly lowered LH levels in F but not in M or AF. The 3.0 cm capsule, with systemic levels of 100 pg E2 /ml serum, was a significant LH suppressor in all groups. The facilitating actions of estradiol benzoate (EB) in M, F, and AF were compared in two trials with 2 different pretreatment regimens of E2 (1.5 cm vs 0.5 cm E2 implant). Under these pretreatment conditions additional exogenous E2 B produced significant elevations in serum LH over pretreatment levels in all 3 groups in both trials. In the second trial, however, M and AF possessed significantly higher LH levels than F, a result that probably reflects differences in the suppressive effects of low doses of E2 between F and AF and M. The time course of luteinizing hormone-releasing hormone (LH-RH)-induced LH was studied in the three groups of monkeys, after a 3-week pretreatment with a low dose of E2 (0.5 cm implant). No significant group differences in pituitary responsiveness were found. These data show that M and AF are less sensitive than F to the long-term feedback inhibition of LH secretion by E2 and that the EB-induced positive feedback responses are present in all three groups. The similar response pattern observed in males and in females treated with testosterone propionate in utero suggests that the E2 -LH negative feedback control system is sexually differentiated as a function of a hormonal preconditioning in fetal life. “Positive feedback,” however, is unaffected unless the higher LH levels in M and AF compared to F after an estrogen challenge are due to factors other than estrogen preconditioning.

Regulation of luteinizing hormone (LH) in the fetal and neonatal lamb. IV. Levels of LH releasing activity in the hypothalamus.

The relative levels of luteinizing hormone releasing factor (LRF) activity in hypothalami of lambs from 9.5 cm crown-rump (C-R) (day 55) to 49 cm C-R (day 148) of prenatal development and in neonates aged 14 to 18 days were determined by an in vitro system. Luteinizing hormone (LH) released from rat adenohypophyses in response to hypothalamic extracts was measured by a sensitive radioimmunoassay specific for murine LH. LRF activity was not detected in hypothalami of fetal lambs, but was readily measurable in hypothalami of neonates of both sexes; however, there was no significant difference between the levels in males and females. Because other studies suggest the existence of hypothalamic control of LH secretion prenatally, the failure to detect LRF activity in fetal hypothalami in the present investigation is attributed either to a loss of LRF activity from the tissue tested as a result of prolonged storage in an unextracted state, or to the possibility that LRF does not accumulate in the hypothalamus o...

Pineal gland, melatonin and the control of luteinizing hormone secretion.

Subjecting adult male rats to pinealectomy causes testicular hypertrophy, enhances the weight of the ventral prostate and of the seminal vesicles and increases pituitary LH stores. These data show that pinealectomy stimulates synthesis and release of pituitary LH and suggest that the pineal gland usually exerts an inhibitory influence on LH secretion. In order to determine whether such an effect of the pineal gland was taking place through a direct action on the pituitary gland or via the mediation of nervous structures, fragments of pineal tissue or crystals of melatonin (a neurohumor specifically synthesized in the gland) were implanted stereotaxically in the median eminence (ME), in the midbrain reticular substance (RS) and in the pituitary gland of castrated male rats. Placement of pineal fragments or of melatonin in the ME and in the RS is followed by a significant reduction of pituitary LH stores. ME and RS implants of melatonin also cause a reduction of plasma LH levels. Melatonin is unable to redu...

Brain receptors sensitive to indole compounds: function in control of luteinizing hormone secretion.

The placement of melatonin and of 5-hydroxytryptophol in the median eminence of castrated male rats is followed 5 days later by a significant decrease in pituitary stores of luteinizing hormone. Pituitary reserve of this hormone is also depleted after the implantation of melatonin, 5-hydroxytryptophol, and 5-methoxytryptophol in the reticular formation of the midbrain. It is suggested that these indole compounds, which are normally synthesized in the pineal gland, may intervene in the control of the secretion of luteinizing hormone, possibly by acting on specific receptors localized in the median eminence and in the midbrain.