Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

Exploratory behaviour and novel predator recognition: behavioural correlations across contexts.

It was hypothesized that the exploratory behaviour of an individual measured in a novel environment could predict its behaviour in response to a novel predator. This study examined novel predator recognition in the western mosquitofish Gambusia affinis, a species with individual differences in risk-taking, activity and exploration in novel environments. Prey responded with characteristic shoaling and avoidance in response to native predators, but did not show characteristic antipredator behaviour towards novel predators. Furthermore, G. affinis exhibited individual-level behavioural correlations across contexts but only when prey were tested with native predators. This could be the result of native predatory selection on behavioural correlations in the prey species.

Single cycle to failure in torsion of three standard and five locking plate constructs.

OBJECTIVES: The biomechanical properties of standard plates and recently designed locking plates were compared in torsion. We hypothesized that titanium (Ti) constructs would have the greatest deformation, and String of Pearls (SOP) constructs the greatest strength and stiffness. METHODS: Dynamic compression plates (DCP), stainless steel (SS) limited contact (LC)-DCP, Ti LC-DCP, locking compression plate (LCP), 10 mm and 11 mm Advanced Locking Plate System (ALPS) 10 and 11, SOP and Fixin plates were applied to a validated bone model simulating a bridging osteosynthesis. Yield torque (strength), yield angle (deformation) and stiffness were compared using one-way ANOVA with post hoc Tukey (p <0.05). RESULTS: The ALPS 11 constructs had significantly greater elastic deformation than all constructs except for the ALPS 10. There were not any differences in strength observed except for the ALPS 10 constructs, which was less than that for the SOP, LCP, DCP and ALPS 11 constructs. No differences in construct torsional stiffness were observed with the SS LC-DCP, DCP, LCP and SOP constructs; however all had greater stiffness than all remaining constructs. The ALPS 10 construct had lower stiffness than all constructs. CLINICAL SIGNIFICANCE: Modulus of elasticity of Ti explains the higher deformation and lower stiffness of these systems, with similar results for the Fixin due to its lower section modulus compared to all other plates. The SOP and standard constructs had surprisingly similar biomechanical properties in torsion. The rationale for selecting these implants for fracture repair likely needs to be based upon their differing biomechanical properties inherent to the diverse implant systems.

Single cycle to failure in bending of three standard and five locking plates and plate constructs.

OBJECTIVE: To evaluate the biomechanical properties of standard and locking plates in bending. We hypothesised that titanium (Ti) constructs would have the greatest deformation and that String of Pearl (SOP) constructs would have the greatest strength and stiffness, and would behave differently compared to plates alone. METHODS: Dynamic compression plates (DCP), stainless steel (SS) limited contact (LC)-DCP®, Ti LC-DCP, locking compression plates (LCP), 10 mm and 11 mm advanced locking plate system (ALPS 10 / 11), SOP and Fixin plates were evaluated individually and as constructs applied to a validated bone model simulating a bridging osteosynthesis. Bending stiffness and strength were compared using one-way ANOVA with post hoc Tukey, and unpaired t-test (p <0.05). RESULTS: The SOP plates had significantly greater stiffness than all other plates; Ti LC-DCP, ALPS 10 and Fixin plates had significantly lower stiffness than all other plates. The SOP constructs had the highest mean bending stiffness, and strength that was significantly different from only the Ti LC-DCP, ALPS 10 and Fixin constructs. The ALPS 10 constructs had the lowest mean bending stiffness, and strength that was significantly different from only ALPS 11 and SOP constructs. Comparison of bending structural stiffness of plates versus constructs showed a significant difference in all plate pairs except for the DCP and ALPS 10. CLINICAL RELEVANCE: Due to differing plate construct properties inherent to these diverse implant systems, identical approaches to fracture management and plate application cannot be applied.

Nicotine blocks the suckling-induced rise in circulating prolactin in lactating rats.

In lactating rats the rapid suckling-induced release of pituitary prolactin into circulating blood is inhibited by a subcutaneous injection of nicotine. This treatment does not block the lesser "stress-induced" rise in prolactin in response to either. Although nicotine may impair milk production by its effect on prolactin release, it does not appear to block milk ejection from the lactating mammary gland.

Electrical activity of the hypothalamus effects of intraventricular catecholamines.

The injection of epinephrine into the third ventricle of the rat brain causes a biphasic elevation and depression in the integrated multiple-unit electrical activity of the median eminence. Activity in the arcuate nucleus decreases after the injection of the catecholamines. These changes in the integrated multiple-unit electrical activity may be related to the secretion of hormones by the anterior pituitary gland.

Recombinant human bone morphogenetic protein-2 enhances osteotomy healing in glucocorticoid-treated rabbits.

The objectives of this study were to evaluate the effect of chronic prednisolone treatment on osteotomy healing in rabbits and to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would enhance healing in the presence of chronic glucocorticoid therapy. Forty-nine skeletally mature, male rabbits were injected with either prednisolone (n = 26; 0.35 mg/kg per day, three times a week) or saline (n = 23). After a 6-week pretreatment period, bilateral ulnar osteotomies were created surgically. One osteotomy was treated with rhBMP-2 (0.2 mg/ml of rhBMP-2, 40 microg of rhBMP-2 total) delivered on an absorbable collage sponge (ACS), whereas the contralateral osteotomy remained untreated. Prednisolone or saline treatment was continued until the rabbits were killed either 6 weeks or 8 weeks after creation of the osteotomy. Osteotomy healing was evaluated by radiography, peripheral quantitative computed tomography (pQCT), torsional biomechanics, and undecalcified histology. Because we observed similar responses to both prednisolone and rhBMP-2/ACS treatment in the 6-week and 8-week cohorts, the results from these time points were combined. Serum osteocalcin and vertebral trabecular bone density were lower in the prednisolone-treated rabbits. Prednisolone treatment dramatically inhibited osteotomy healing. In the untreated ulnas, callus area and torsional strength were 25% and 55% less, respectively, in the prednisolone-treated rabbits than in the saline group (p < 0.001 for both). rhBMP-2/ACS enhanced healing in both the prednisolone- and the saline-treated groups, although the effect was larger in the prednisolone-treated rabbits. In the prednisolone-treated rabbits, callus area and torsional strength were 40% and 165% greater (p < 0.001 for both), respectively, in osteotomies treated with rhBMP-2/ACS compared with the contralateral, untreated osteotomies. Histological evaluation confirmed that osteotomy healing was inhibited by prednisolone and accelerated by rhBMP-2/ACS. In summary, a single application of rhBMP-2/ACS counteracted the inhibition of osteotomy healing caused by prednisolone exposure. These results suggest that rhBMP-2/ACS may be a useful treatment for enhancing fracture healing in patients who are undergoing chronic glucocorticoid therapy.

A detailed characterization of the proestrous luteinizing hormone surge.

Four-day cycling rats were kept in a room with the light on from 0500-1900 h. Plasma LH concentrations in blood withdrawn through atrial cannulas at hourly intervals from 1400-2000 h on proestrus were very similar to serum LH concentrations in blood collected from uncannulated rats by decapitation at these times. Additional cannulated rats were bled (0.1 ml) at 5 min intervals from 1400-1600, 1600-1800, or 1800-2000 h. After each bleeding, 0.1 ml of heparinized saline was injected through the cannula. Following a rise (rate unknown) to detectable levels of about 200 ng/ml, plasma LH displayed a rapid linear increase to 1538 +/- 118 ng/ml, starting between 1445 and 1650 h and lasting 20 to 50 min. Over the next 110 min plasma LH at first rose erratically by about another 200 ng/ml and then fluctuated around an apparent plateu. It then dropped rapidly but the declines were commonly interrupted by one or more rapid increases in plasma LH. A generalized pattern of the proestrous LH surge has been constructed from the data.

Effects of intravenous infusion of catecholamines on rat plasma luteinizing hormone and prolactin concentrations.

UNLABELLED: Catecholamines were infused through an atrial cannula in unanesthetized rats on the afternoon of proestrus and blood was withdrawn through a second cannula for radioimmunoassay of LH and prolactin. Infusion of epinephrine, but not of norepinephrine or dopamine, blocked spontaneous pituitary LH release and ovulation. Ultimately, this effect appears to be exerted on the brain and not on the pituitary or through changes in pituitary blood flow. Pituitary LH release in response to exogenous LHRH, when administered in an amount that simulated the proestrous LH surge in phenobarital-treated rats, was unaltered by epinephrine infusion. In addition, epinephrine infusion did not alter the timing of the rise in plasma prolactin. Infusion of dopamine blocked the spontaneous rise in plasma prolactin and depressed basal prolactin levels. After the end of infusion, plasma prolactin rose rapidly. Infusion of norepinephrine or epinephrine partially suppressed the prolactin rise but only after 2 h of infusion. THE RESULTS: 1) point out the possibility that chronic release of epinephrine from the adrenal medulla may be involved in phenomena in which "stress" inhibits reproductive function; and 2) are consistent with the view that dopamine, but not norepinephrine, may be PIF.

Simulation of the early phase of the proestrous follicle-stimulating hormone rise after infusion of luteinizing hormone-releasing hormone in phenobarbital-blocked rats.

Four-day cycling rats were kept in a room with the lights on from 0500-1900 h. Plasma FSH concentrations in blood withdrawn through atrial cannulas at hourly intervals from 1400-2000 h on proestrus were very similar to serum FSH concentrations in blood collected by decapitation. Additional cannulated rats were bled at 20 min intervals from 1400-1600, 1600-1800, or 1800-2000 h. In most rats, plasma FSH concentration rose gradually to approximately three times pre-rise levels by 1900 h. It then decreased slightly by 2000 h. Injection of an ovulation-blocking dosage of phenobarbital at 1345 h blocked the FSH rise. Rapid injection of 124 or 1240 ng of LHRH at 1300 h did not elevate plasma FSH by 1315 h but the 1240 ng dose did by 1400 h. Phenobarbital injection at 1230 h did not alter this response. In additional blocked rats, blood was rapidly withdrawen through one of two indwelling atrial cannulas while LHRH was infused at a constant rate through the other. Administration of LHRH by infusion was much more effective in elevating plasma FSH than was rapid injection of the releasing hormone. The pattern of plasma FSH concentration after infusion of about 50 ng of LHRH per hour from 1500-1810 h and then about 12 ng of LHRH per hour from 1810-1920 h was remarkably similar to that of the spontaneous FSH rise. These experiments imply that the early phase of the FSH surge (the one associated with the proestrous LH surge) is caused by a properly timed, nearly constant-rate release of LHRH for about 3 h (beginning about 1500 h of proestrus) followed by a period of diminished LHRH release.

Simulation of the proestrous luteinizing hormone (LH) surge after infusion of LH-releasing hormone in phenobarbital-blocked rats.

Four-day cycling rats were kept in a room with the lights on from 0500-1900 h. Injection of an ovulation-blocking dose of phenobarbital at 1230 h on proestrus did not alter the rise in plasma LH concentration in response to rapid injection of 12.4, 124, or 1240 ng of LHRH at 1300 h. In additional blocked rats, blood was rapidly withdrawen through one of two indwelling atrial cannulas while LHRH was infused at a constant rate through the other. Administration of a given amount of LHRH by slow infusion was much more effective in elevating plasma LH than was rapid injection of the same amount of releasing hormone. The pattern of plasma LH concentration after infusion of approximately 50 ng of LHRH per hour from 1500-1810 h was remarkably similar to that of the spontaneous LH surge, i.e., a gradual rise in plasma LH concentration followed by a steep linear increase to high levels which remained elevated for a period of approximately 2 h before declining rapidly soon after the end of infusion. In rats given a second 3 h infusion of LHRH at the same rate, from 2200 to 0100 h, a different response pattern was seen: the initial increase in plasma LH was greater, but the linear rise, which ensued after a lag period of similar duration (about 45 min), was less marked. Prolongation of the first infusion beyond 1800 h did not prolong the plateau: plasma LH levels declined before the infusion was terminated. This decline was less rapid than that seen at the end of a spontaneous LH surge, which in turn was less rapid than that seen after termination of a 3 h and 10 min infusion starting at the same time (1500 h), suggesting that both LHRH release and pituitary responsiveness are diminished (but not abolished) at this time. These findings clearly indicate that, in phenobarbital-blocked proestrous rats, the major part of the proestrous LH surge (including rising and plateau phases) can be simulated by a constant-rate infusion of about 150 ng of LHRH over the 3 h and 10 min period beginning at 1500 h. Since the data also suggest that LHRH release is reduced and/or occurs sporadically during the terminal phase of the surge (when plasma LH levels are declining), these experiments imply that the LH surge is caused by a properly timed, nearly constant-rate release of LHRH for about 3 h (beginning about 1500 h of proestrus) followed by a period of diminished LHRH release.

Changes in plasma luteinizing hormone-releasing hormone and gonadotropin concentrations during constant rate intravenous infusion of luteinizing hormone-releasing hormone in cyclic rats.

Further analysis has been made of the response of the rat pituitary gland to LHRH during the 4-day estrous cycle. LHRH was infused iv at a constant rate (50 ng/h) into phenobarbital-treated rats at different times during the estrous cycle. Infusion at this rate in proestrous rats simulates the rising and plateau phases of the spontaneous proestrous surges of LH and FSH in plasma. Plasma LH rose to similar heights during the "initial phase" of LH release (during the first 40 min of infusion) on the afternoons of estrus, diestrous day one, and proestrus and during the morning of proestrus. The increase during the afternoon of diestrous day two was significantly less than that in all the other groups. A similar response was seen in the case of FSH release. A "rapid rising" or "augmented" phase of LH release (during 40-120 min of infusion) was present in all groups and the magnitude of the response was greatest during the afternoon of proestrus. In the case of FSH, an augmented phase of release started 60 min after the start of infusion, and the response during the afternoon of proestrus was slightly greater than the responses measured at the other times tested. The responses on diestrous day one were not altered when phenobarbital was omitted or when rats were ovariectomized shortly before LHRH infusion. Other differences in the LH and FSH responses during both initial and augmented phases of release were seen in rats tested at different times during the estrous cycle with an LHRH infusion rate which caused a supraphysiological response on proestrus. The results suggest that 1) the initial rising phases in plasma LH and FSH during the spontaneous surges during proestrus are not the result of an increase in pituitary responsiveness to LHRH during the estrous cycle, 2) augmented phases of LH and FSH release can be elicited on all days of the estrous cycle, and 3) the increases in magnitude of the augmented phases of LH and FSH release on proestrus, as compared to those on other days of the cycle, are the result of an increase in pituitary responsiveness to LHRH during the estrous cycle.

Catecholestrogens and release of anterior pituitary gland hormones. I. Luteinizing hormone.

We investigated the effects of peripheral administration of 17 beta-estradiol (E2), estrone (E1), and the catecholestrogens, 2-hydroxyestradiol (2-OHE2) and 2-hydroxyestrone (2-OHE1), on anterior pituitary gland LH release in the prepuberal rat. Steroids in oil were injected sc into 25-day-old female and 35- to 40-day-old male rats. The injection of E2, E1, or 2-OHE2 caused a surge in serum LH levels in female rats 48 h later, during the after hours. Only E1 induced a LH surge 24 h after injection. The positive effects of 2-OHE2 in the females were only observed if a massive dose was administered, the steroid was injected on 2 consecutive days, or E2 or progesterone was given to 2-OHE2-primed rats. The 2-OHE1 was totally ineffective in causing a serum LH surge under a variety of experimental protocols. In male rats, the injection of any one of the four steroids decreased serum LH levels. Even the injection of E2 or 2-OHE2 for 2 days or the injection of E2 in 2-OHE2-primed rats failed to elevate the serum LH concentration in male rats. The results suggest that 2-OHE2 and E1 could play a role in the preovulatory release of LH in the female; 2-OHE2 and 2-OHE1 could play a role in the negative feedback control of LH release in the male.

Catecholestrogens and release of anterior pituitary gland hormones. II. Prolactin.

We investigated the effects of the peripheral administration of 17 beta-estradiol (E2), estrone (E1), and the catecholestrogens, 2-hydroxyestradiol (2-OHE2) and 2-hydroxyestrone, (2-OHE1), on anterior pituitary gland PRL release in the prepuberal rat. Steroids in oil were injected sc into 25-day-old female and 35- to 40-day-old male rats. The injection of E2, E1, or 2-OHE2, but not of 2-OHE, caused a surge in serum PRL levels in female rats 48 h later, during the afternoon hours. Only E1 induced a PRL surge 24 h after injection. In male rats, the injection of E1 or 2-OHE2, but not of 2-OHE1, elevated serum PRL levels on a chronic basis. The results suggest that 2-OHE1 plays no discernible role in PRL release in either sex, but that 2-OHE2 might play a role in the tonic release of PRL in the male and in the preovulatory release of PRL in the female.

Hypothalamic-pituitary interactions during the periovulatory secretion of follicle-stimulating hormone in the rat.

We investigated the importance of anterior afferents to the medial basal hypothalamus (MBH) on the increases in plasma FSH during the periovulatory period in the 4-day cyclic rat. We served the anterior connections to the MBH either at 1200 h on proestrus (before the time of onset of the normal spontaneous LH surge in plasma and the associated first phase of FSH release) or near the end of the LH surge and first phase of FSH release at 2000 h on proestrus (before the onset of the second or selective phase of FSH release). Analyses of FSH and LH in blood collected through indwelling atrial catheters or from the trunk after decapitation showed that anterior deafferentation of the MBH at 1200 h on proestrus blocked the proestrous LH surge, the elevations in plasma FSH during proestrus and estrus, and ovulation. In contrast, when brain surgery was delayed until 2000 h on proestrus, the second phase of FSH release and ovulation occurred. In rats with retrochiasmatic transections made at 1200 h, a constant rate iv infusion of LHRH from 1500-1800 h on proestrus restored the LH surge, both phases of increased plasma FSH, and ovulation. The results suggest that 1) the prevolutory LH surge and the first phase of FSH release are dependent on rostral afferents to the MBH which result in hypothalamic LHRH release and 2) the role of rostral afferents to the MBH in the second phase of FSH release is solely to result in hypothalamic LHRH release during proestrus.

The response of splenic lymphocytes removed from hypophysectomized-orchidectomized hamsters to phytohemagglutinin correlates with somatic growth but not with circulating prolactin levels.

To examine the relationship between PRL and the mitogenic capacity of lymphocytes, we studied the relationships among circulating PRL levels, somatic growth, and the response of splenic lymphocytes to the mitogen phytohemagglutinin (PHA) in hamsters. In the first experiment, no differences were observed in the PHA responses of lymphocytes removed from intact or hypophysectomized-orchidectomized hamsters. No relationships were observed between circulating PRL levels and either the PHA responses or somatic growth. However, significant positive correlations were observed between the somatic growth of intact or hypophysectomized-orchidectomized hamsters and the PHA responses (r = 0.741; P less than 0.01 for intact hamsters; r = 0.642; P less than 0.01 for hypophysectomized-orchidectomized hamsters). In three subsequent experiments we tested the effects of placing muscle or hypophysial allografts in hypophysectomized-orchidectomized hamsters on somatic growth, the PHA responses, and circulating PRL levels. Neither type of allograft altered the somatic growth of hypophysectomized-orchidectomized hamsters. The hypophysial allografts did elevate serum PRL levels. In all experiments the responses of splenic lymphocytes to PHA showed a significant positive correlation with somatic growth, but not with serum PRL levels. These results minimize a role of PRL in this particular lymphocyte response. The results suggest that a strong correlation exists between mechanisms responsible for somatic growth in hypophysectomized-orchidectomized hamsters and the immune status, as determined by the response to PHA, of the animals. This relationship also may exist in intact hamsters.

Luteinizing hormone (LH)-releasing hormone: chronic effects on LH and follicle-stimulating hormone cells and secretion in adult male rats.

We investigated whether chronic administration of LHRH to normal adult rats could increase the percentages of anterior pituitary gland (APG) cells that contain immunoreactive LH and/or FSH and gonadotropin secretion. Vehicle or 1 microgram LHRH was injected sc twice daily for 6 days, and rats were decapitated 16 h after the last injection. Treatment with LHRH caused nearly a doubling in the numerical density of LH and FSH cells and in the percentage of APG cells that contained LH or FSH. It also caused a shift in the gonadotroph population from LH and LH/FSH cells to LH/FSH cells. It did not change the mean size of gonadotrophs or APG weight. These changes at the light microscopic level were not accompanied by any apparent changes in LH cells at the ultrastructural level. However, they were accompanied by an approximate doubling of the basal serum LH and FSH concentrations, an increase in the APG FSH concentration, and an increase in the basal FSH release rate (measured in vitro). The results indicate that exogenous LHRH can be administered to increase numbers of gonadotrophs in the APG, synthesis of FSH in gonadotrophs, and basal serum LH and FSH concentrations.

Gonadotropin-releasing hormone-induced accumulation of follicle-stimulating hormone beta-subunit messenger ribonucleic acid in adenohypophysial cells developing in an ectopic position.

We investigated the influence of LHRH on the accumulation of FSH beta messenger RNA (mRNA) in anterior pituitary glands removed from hamster pups less than 36 h old and transplanted beneath the renal capsules of adult male hamsters (hosts). Three experiments were performed in which some hosts were injected sc with LHRH (1 microgram/injection) and others were injected with vehicle. Injections were begun in the afternoon of the day of transplantation (day 1) and were given at 0800 and 1700 h for 6 days and at 0800 h on the eighth day. An additional experiment was performed in which adult male hamsters not bearing allografts were injected with the same regimen of LHRH or vehicle. The hamsters were decapitated on the eighth day of the study, 2 h after the last injection. The allografts, adenohypophyses of the hosts, adenohypophyses of hamsters without allografts, and adenohypophyses of normal adult male rats were removed and frozen on dry ice immediately. Additionally, adenohypophyses were collected from hamster pups less than 36 h old and 8 and 15 days of age. Total RNAs from some pooled specimens were electrophoresed on a formaldehyde-agarose gel. After transfer to Nytran, the RNAs were hybridized sequentially to complementary DNAs for rat FSH beta and hamster beta-actin. The rat FSH beta complementary DNA probe hybridized to a single RNA (approximately 1.7 Kb) in rat adenohypophyses. It predominantly hybridized to RNA of approximately 1.7 Kb from hamster adenohypophyses. Sometimes it hybridized to RNAs ranging in size from 0.5 Kb to 1.7 kb. The hybridization signals for all samples obtained from dot blot analyses were quantitated and normalized to the signals for beta-actin. The hybridization signals obtained from adenohypophyses of hamsters of different ages increased from 36 h of age to adulthood. The hybridization signal obtained from adenohypophyses of hamsters less than 36 h old (the same age as the donor hamsters) was similar to the hybridization signal obtained from allografts in vehicle-treated hamsters. The relative levels of FSH beta mRNA in allografts of LHRH-treated hosts were: 1) greater than the relative levels in adenohypophyses of hamsters less than 36 h old (P less than 0.05) and in allografts in vehicle-treated hamsters (P less than 0.05), 2) greater than the relative levels in adenohypophyses of 8-day-old hamsters (P less than 0.05), and 3) not different compared to the relative levels in adenohypophyses of 15-day-old hamsters and adult male hamsters.(ABSTRACT TRUNCATED AT 400 WORDS)

Luteinizing hormone (LH)-releasing hormone: effects of induction of LH, follicle-stimulating hormone, and prolactin cell differentiation.

We investigated the influence of LHRH on the differentiation of gonadotrophs and lactotrophs in fetal pituitary glands transplanted beneath the renal capsules of adult hypophysectomized-orchidectomized hamsters (hosts). Hypophyses were removed from hamster fetuses at a gestational age of 14 days. Some of these were immediately fixed in Bouin's solution, and others were transplanted into the hosts. The hosts were injected sc twice daily with 1 microgram LHRH or vehicle for 16 days. Six hosts in each group were killed by decapitation 16 h after the last injection. Six 14-day-old normal male hamsters (age-matched to correspond to the age of the allografts at the time of the hosts' decapitation) also were decapitated. Sections of hypophyses in situ from fetal hamsters, from 14-day-old controls, and from allografts in each group were stained for LH, FSH, or PRL and with hematoxylin. No PRL-containing cells and very few LH or FSH cells (less than 0.025% of the adenohypophysial cell population) were observed in fetal pituitary glands. In allografts from the vehicle-treated hosts, 21.1% of adenohypophysial cells contained LH, but only 1.8% contained FSH. In allografts from LHRH-treated hosts, 28.0% and 22.9% of the adenohypophysial cells contained LH and FSH, respectively. Adenohypophyses that developed for the same length of time in situ had smaller percentages of adenohypophysial cells containing LH (23.8%) and FSH (15.5%) than the LHRH-treated group. LH-containing cells in allografts in the vehicle-treated hamsters, but not in the LHRH-treated animals, were reduced in size compared to those measured in situ. The number of lactotrophs in all allografted tissue was markedly reduced compared to that of lactotrophs in situ, and injection of LHRH into hamsters with allografts did not alter the percentage of adenohypophysial cells that were lactotrophs. These results suggest that in the hamster LHRH 1) plays an important role in stimulating the formation of immunoreactive FSH in the pituitary gland, 2) can increase the number of gonadotrophs that develop during the neonatal period, and 3) plays a role in controlling the size of gonadotrophs during development. The results also suggest that the development of lactotroph cell number requires close proximity to the hypothalamus and/or exposure to a neonatal environment. We found no evidence to support the view that LHRH, LH, or FSH stimulates immunoreactive lactotroph differentiation.

Luteinizing hormone (LH)-releasing hormone: effects on maintenance of immunoreactive follicle-stimulating hormone and LH in adenohypophysial cells.

We investigated the importance of LHRH on the maintenance of FSH and LH immunoreactivity in gonadotrophs. Hypophysectomized orchidectomized hamsters (hosts) each received an allograft of a 7-week-old male hamster pituitary gland beneath their right renal capsule. Starting 6 days after transplantation, hosts were injected sc, twice daily with 1 micrograms LHRH or vehicle for 16 days. Twelve hosts in each group were killed by decapitation 16 h after the last injection. Allografts from six of the hamsters in each group and pituitary glands in situ from 10-week-old normal males were prepared for histological examination. Sections of tissue were stained for FSH or LH and with hematoxylin. Allografts from the remaining hamsters were homogenized to measure FSH and LH concentrations. In allografts from the vehicle-treated hosts, 22.8% of adenohypophysial cells stained for LH, while only 16.9% stained for FSH. In allografts from LHRH-treated hosts, 22.6% and 23.8% of the adenohypophyses cells stained for LH and FSH, respectively. Adenohypophyses that developed for the same length of time in situ had 24.8% and 24.1% of the cells staining for LH and FSH, respectively. Matching of some of the FSH and LH cells in serial flip-flopped sections of tissue from all hamsters revealed that many if not all gonadotrophs contained LH. LH- and FSH-containing cells in allografts were similar in size and shape, but were smaller and more circular in profile than those observed in situ. Treatment of hosts with LHRH did not alter gonadotroph size or shape, but it did reduce allograft LH concentration and elevate the serum FSH concentration compared to that in the vehicle-treated hamsters. These results suggest that in the hamster LHRH 1) plays a major role in maintaining FSH immunoreactivity in adenohypophysial tissue, 2) does not play a role in maintaining numbers of immunoreactive LH cells in adult adenohypophysial tissue, and 3) functions to maintain FSH synthesis at least in part in cells that contain LH.