Effects of Starvation in Rats on Serum Levels of Follicle Stimulating Hormone, Luteinizing Hormone, Thyrotropin, Growth Hormone and Prolactin; Response to LH-Releasing Hormone and ThyrotropinReleasing Hormone G. A. CAMPBELL,1 M. KURCZ,2 S. MARSHALL, AND J. MEITES 3 Department of Physiology, Neuroendocrine Research Laboratory, Michigan State East Lansing, Michigan 48824

fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups of rats, FSH and PRL rose in acutely but not in chronically starved rats, and GH was not elevated in any group. The increases in serum LH, FSH, TSH and prolactin in response to LHRH + TRH injection in acutely or chronically starved rats were equal to or greater than in the ad libitum fed controls. These data indicate that severe reductions in food intake result in decreased release of at least 5 anterior pituitary hormones, and this is due primarily to reduced hypothalamic stimulation rather than to inability of the pituitary to secrete hormones. (Endocrinology 100: 580, 1977)

ABSTRACT. Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of VA ad libitum food intake (chronically starved), 7 days complete

food removal and 2 weeks of lA ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum

R

EDUCED food intake has been reported to result in decreased secretion of anterior pituitary (AP) hormones (1-10), accompanied by a reduction in weight and function of target organs. The term "pseudohypophysectomy" sometimes has been applied to this state (1,10). Inanition or absence of dietary protein in rats was observed to inhibit markedly reproductive functions without reducing AP content of gonadotropReceived March 22, 1976. 1 Research Associate, Department of Physiology, Michigan State University. 2 Research Associate, Department of Physiology, Michigan State University. Permanent address: Department of Biochemistry, National Institute of Health, Budapest, Hungary. 3 Aided in part by NIH research grants AM04784 from the National Institute of Arthritis, Metabolism, and Digestive Diseases, and CA10771 from the National Cancer Institute. We are indebted to NIAMDD and Dr. A. Parlow for the RIA kits used in this study.

University,

ins (11), to depress pituitary-thyroid activity (12,13), to decrease pituitary prolactin content (9) and to lower AP and blood GH levels (14,15). Adrenal weight was decreased during moderate underfeeding but was increased during severe undernutrition (9). Few reports have appeared as yet on blood levels of AP hormones during restricted food intake. The mechanisms responsible for the apparent reduction in AP hormone secretion during inanition have received but little attention thus far, and for many years it was assumed that this was a direct consequence of the deficiency of nutrients on AP function (16). However, there are several indications that this assumption may be incorrect and that the primary fault lies in the central nervous system. Thus, we have reported that reduced food intake in rats results in decreased hypothalamic content of GRF, LRF,

580

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STARVATION EFFECTS ON AP HORMONES

and FRF as measured by bioassays (14, 17-19). Also, castration (9,20,21) and constant light (18,22) were observed to counteract the inhibitory effects of inanition on AP gonadotropin release and on gonadal function. In order to define more clearly the relationship between restricted food intake and AP function, and to clarify further the mechanisms responsible for diminished hormone secretion, we determined the changes in serum levels of LH, FSH, TSH, GH, and PRL during acute and chronic starvation and after refeeding, and tested the AP response to injections of synthetic LHRH and TRH. Materials and Methods Animals Adult male Sprague-Dawley rats were obtained from Spartan Research Animals, Inc. (Haslett, Mich.) and averaged about 300 g at the onset of this study. They were housed in individual steel cages in a temperature controlled (25 ± 1 C) and artificially illuminated (from 0500 to 1900 h daily) room and were given food and water ad libitum. All cages had wire screen floors to prevent coprophagia. The average daily consumption of pelleted food (Purina Lab Chow) was measured, and the rats were then separated into groups of approximately equal average-

body weight and treated as follows: no food for 7 days (acutely starved, AS); no food for 7 days followed by lk of initial average food intake for 2 weeks (chronically starved, CS); no food for 7 days followed by lA initial average food intake for 2 weeks and then restored to ad libitum feeding for 7 days (refed group, R); ad libitum food intake (controls, C). Blood samples were obtained by orbital sinus puncture under light ether anesthesia during all dietary regimens, and the serum was separated by centrifugation and frozen for assay. When rats were killed, blood samples were obtained from the trunk after decapitation to compare values for hormone levels in the absence of etherization and orbital sinus puncture. Animals from all groups were autopsied and the AP glands, adrenals, gonads and accessory reproductive organs were removed and weighed. A measure of the amount of seminal fluid was obtained by

581

crushing the seminal vesicles and expressing the contents followed by a second weight determination of the seminal vesicles. LHRH + TRH administration Rats from all groups received a single ip injection of 0.85% NaCl containing a mixture of 1 fxg synthetic TRH/300 g BW (generously provided by Dr. K. Folkers, Institute for Biomedical Research, University of Texas, Austin, Texas) and 0.5 /ug synthetic LHRH/300 g BW (kindly provided by Abbott Laboratories, N. Chicago, 111.), 4 h after a pre-treatment blood sample was taken at 0900 h. The releasing hormones were used in combination so as to study the response of at least 4 of the AP hormones under consideration in the same animals simultaneously. Post-treatment blood samples were collected at 30, 60, and 150 min after LHRH + TRH administration, and the serum was frozen and stored for hormone assay. Hormone assays Serum was separated fron the blood samples after coagulation at 4 C, and stored at — 20 C until radioimmunoassayed for LH, FSH, TSH, GH and PRL. Serum LH and PRL were assayed by the methods of Niswender et al. (23,24), and FSH, GH, and TSH were assayed according to the directions provided with the NIAMDD RIA kits for those hormones. Concentrations of PRL, LH, FSH, GH and TSH in the serum were expressed in terms of NIAMDD rat PRL-RP-1, LH-RP-1, FSH-RP-1, GH-RP-1, and TSH-RP-1, respectively. All results were subjected to analysis of variance and the effects of diets and the releasing hormones were evaluated by multiple range testing according to the method of Student-Newman-Keuls (25). The terms "significant" and "very significant" wherever used always signify P < 0.05 and P < 0.01, respectively. Results

Organ weights The changes in body weight and organ weights are summarized in Table 1. The average body weight of AS rats was about 75% of that of C rats, and CS rats weighed about 65% of C rats. The body weight of

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Endo • 1977 Vol 100 • No 2

CAMPBELL ET AL. TABLE 1. Effects of restricted food intake on body and organ weights Mean orj;an weight Seminal Testes

AP

Dietary regi-

No. of

final

RW

RW

change

men

rats

(g)

(%)

C1 AS CS R R3

23 15 8 9 5

349 265 214 347 331

-24 -36 -1 -5

Absolute (mg) 9.2

7.3* 6.8f 9.3 8.7

gRW

Absolute (mg)

2.6 2.8 3.2 2.7 2.6

3,733 3,655 3,035 3,314t 3,122

/100

Seminal fluid

ves icles

/100 gHW

1,070 1,379 1,418 955 943

Absolute (mg)

gRW

230.0 165.7t 165.1 160.4 151.2

65.9 62.5 77.2 46.2 45.7

Absolute (mg)

/100

944 429 110

672f 968

Prostate

gRW

Absolute (mg)

270 162 51 194 292

390.0 279.2 173.3 280.81 381.8

/100

Adrenals

gRW

Absolute (mg)

gRW

111.8 105.3 81.0 80.9 115.3

55.7 60.72 48.4t 45.7 51.2

16.0 22.9 22.7 13.2 15.5

/100

/100

* and t, respectively, indicate upper boundary of significant (P < 0.05) and very significant (P < 0.01) decreases in weight as compared to controls. C refers to ad libitum fed controls; AS (acutely starved) refers to rats deprived of all food for 7 days; CS (chronically starved) refers to rats that were fed Vi the ad libitum level for 2 weeks after 1 week without food; R (refed) refers to CS rats that were returned to ad libitum intake for 1 week. 2 This weight was significantly higher than that of controls. 3 This group was refed for 2 weeks, but was not used to provide blood samples. 1

CS rats was restored to normal after 1 week of full feeding. The adrenal glands were enlarged in AS rats, both in absolute terms and relative to body weight, while in CS rats the adrenals were enlarged only with respect to body weight and were smaller than normal in absolute terms. The gonads, accessory reproductive organs, and volume of seminal fluid were diminished in

all starved groups. The decreases were most severe in CS rats. The order of this decrease, ranging from most to least affected was: seiminal fluid, prostate, seminal vesicles and testis. The size of the testis was reduced only by 20% during starvation, and was increased relative to body weight. The APs of all starved animals were decreased in absolute size, and the reduction was greatest

TABLE 2. Effects of restricted food intake on AP hormone responses to LHRH + TRH Post-treatment levels (ng/ml) Dietary regimen

Cf

1 1C Li. t^dLlllCll L

Hormone

levels (ng/ml)

FSH LH TSH

30 min

60 min

150 min

264.5 ± 17.3 53.0 ± 9.7 1,142.9 ± 129.2 30.1 ± 2.4 24.3 ± 5.3

225.4 ± 13.1 12.1 ± 1.7

GH

205.7 ± 11.8* 18.4 ± 1.4 1,199.0 ± 68.6 34.4 ± 2.0 127.7 ± 27.5

AS

FSH LH TSH PRL GH

139.1 ± 8.2 4.7 ± 0.9 371.2 ± 47.1 16.0 ± 1.8 56.2 ± 13.5

15.7 241.5 ± 110.3 ± 13.6 9,324.1 ± 1,001.0 23.3 ± 2.0 32.6 ± 5.4

221.2 86.6 2,856.7 35.0 19.7

± 11.3 ± 7.4 ± 389.6 ± 4.1 ± 2.7

239.4 ± 13.2 12.7 ± 1.9 —

CS

FSH LH TSH PRL GH

176.6 ± 26.2 6.6 ± 0.8 307.6 ± 26.8 16.3 ± 1.4 48.0 ± 7.7

256.2 74.7 3,672.0 11.4 45.4

± ± ± ± ±

47.2 13.5 342.9 1.5 7.4

217.5 ± 37.9 57.6 ± 7.8 1,318.7 ± 117.0 14.4 ± 1.2 38.0 ± 5.4

212.6 ± 30.2 12.7 ± 1.7

FSH

527.9 42.9 550.4 97.3

542.3 ± 97.0 ± 2,145.5 ± 36.9 ±:

75.2 8.7 195.9 6.0

PRL

R

LH TSH GH

± 73.1 ± 3.9 ± 27.9 ± 25.4

237.8 125.5 4,752.3 37.3 95.2

± ± ± ± ±

15.1 13.2 467.0 2.3 13.5

503.2 87.8 720.5 27.7

± 79.3 ± 10.9 ± 47.2 ± 9.1

29.4 ± 4.2

33.4 ± 6.1

52.3 ± 6.8 553.5 ± 64.9 27.9 ± 2.8 27.5 ± 2.6

* Mean ± SEM. f Notations are identical to Table 1.

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STARVATION EFFECTS ON AP HORMONES in chronic starvation, but they were always larger than in ad libitum-ied rats when considered relative to body weight. The APs of the refed rats weighed the same as those of the controls. The testes and seminal vesicles of refed rats did not return to normal size after 2 weeks of refeeding. Serum hormone levels The changes in circulating hormone levels after restricted food intake are summarized in the first column of Table 2. All serum AP hormone levels tested were strongly reduced after 7 days of complete starvation. The extent of this decline was different for each hormone, as can be seen more clearly in Fig. 1. This shows the alterations in hormone levels under all treatments relative to the levels found in the ad libitumied controls. The order of the decreases from most to least affected was: LH, TSH, GH, PRL, and finally FSH. In the 7 day AS rats, LH levels were reduced by about 75% as compared with those of the controls, whereas FSH was decreased by only 32% of the control value. TSH, PRL and GH were reduced by 69, 54, and 56%, respectively, as compared to control levels. The hormone levels after CS were not significantly dif-

ferent from those found after AS, with the possible exception of FSH. Refeeding for 7 days after CS produced elevations in circulating LH and FSH to values well above those for controls, i.e., by 133 and 157%, respectively. In contrast, 7 days of refeeding elevated PRL only to the level found in the controls in serum obtained by decapitation (not shown), returned serum GH to a value that was lower, although not significantly so, than in the controls, and failed to restore TSH to control levels. Although not documented herein, the effects of these dietary regimens on blood values obtained from the orbital sinus were essentially duplicated in blood collected from decapitated rats. AP response to LHRH + TRH A comparison of the AP hormone responses from the different groups to a single injection of LHRH + TRH is also shown in Table 2. In ad libitum-ied rats there was an increase in LH, FSH, and TSH, but not in GH and PRL. In AS rats, significant elevations appeared for all hormones except GH. In CS rats, GH, PRL, and FSH failed to rise significantly. Only TSH rose sig-

200

GH

c

AS cs

R

c

AS cs it

c

AS

cs

583

F I G . 1. Comparison of the effects of restricted food intake and refeeding on serum hormone levels with levels found in fully-fed controls. T h e different dietary regimens are designated by the following notations: C (controls) = rats fed a d libitum: AS (acutely starved) = rats given no food for 7 days; CS (chronically starved) = rats given VA of ad libitum food intake for 2 weeks after 7 days without food; R (refed) = rats returned to ad libitum regimen after 14 days of chronic starvation. T h e n u m b e r of rats in each group is as listed in Table 1. T h e vertical bars represent 1 standard error of the mean.

C AS CS «

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Endo • 1977 Vol 100 . No 2

CAMPBELL ET AL. NG/ML

OF

NG/ML

BASAL

10.000

OF BASAL

TSH

2000

2000

100

5.000 1000

1000

50

100 B

3O 6O 15O

B

100

B 30 6O

3O 6O 15O

FSH

i

r

200

IAS

/

\ c

200 20

AS

PRL

40

500

B 30' 6O

/ / ' K

/

/

1

I

f -T c s

V

c

L

IT

100

V 100

1

0 B 30 60 150

B 30 60 CO

I

B 30 60

cs

i

B

FIG. 2. Changes in serum AP hormone levels in response to LHRH + TRH administration. A single injection was given containing 1 /ug TRH and 0.5 ^g LHRH/300 g BW. The absolute values are given on the left side of each inset, while the changes relative to the pre-injection level are given on the right side. The notations are the same as in Fig. 1. B = before injection. The number of rats in each group is as listed in Table 1. The vertical bars represent 1 standard error of the mean.

nificantly in the refed rats. Serum GH was, in general, depressed at all time periods, in all groups, after LHRH + TRH administration. The response curves for each hormone except GH are shown in Fig. 2 both in terms of absolute values on the left side of each panel, and as the change in concentration relative to pretreatment levels on the right side. The extent to which the various hormones were elevated over the pre-treatment values was always greatest in rats given no food for 7 days; the next greatest such rise was found in CS rats.

Hormone levels rose the least in R rats except for TSH which increased to the same degree as in the ad libitum fed controls. A more detailed description of the patterns of individual hormonal responses is given below. LH response All groups demonstrated an increase in serum LH in response to LHRH + TRH administration. In AS and C rats, circulating LH levels rose to the same values after 30 min. Since the pretreatment levels of LH

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STARVATION EFFECTS ON AP HORMONES were lower in AS rats, the serum rise was greater (about 25x) than for C rats (about 7x). Although serum LH was significantly less in the CS rats at 30 min than in the AS and C rats, the change from pretreatment levels in CS rats was greater (about 12x) than for C rats. By 60 min circulating LH declined to lower but not to pre-treatment levels in all groups, and by 150 min returned essentially to pre-treatment values. FSH response Stimulation of FSH release by LHRH + TRH was much more limited than for LH, but the same order of responsiveness was observed, i.e., AS > CS > C > R at 30 min. AS rats demonstrated a clearcut rise in FSH levels that persisted throughout 150 min. In contrast, the ad libitum fed group showed a significant rise only at 60 min and the FSH levels returned to pretreatment values by 150 min. CS rats responded to LHRH + TRH but the elevation was found not to be significant due to the large variance observed in this group. The R group FSH values were high and these were not further elevated by the LHRH+ TRH treatment. TSH response Although the elevation in response to LHRH + TRH was of greater absolute as well as of relative magnitude in AS rats than for the fully-fed controls, and the elevations were of shorter duration for all groups than those observed for LH, the TSH responses were essentially similar to that found for LH. Although the TSH and LH responses of R rats were less than those of C rats, the relative change in TSH levels in R rats was equal to that of C rats, whereas the relative change in LH levels was less in R rats than in C. PRL response LHRH + TRH did not stimulate PRL release in C or CS rats, but caused a 2-fold

585

increase in AS rats at 60 min. In contrast to LH and TSH, there was no PRL response to LHRH + TRH when blood was obtained by decapitation. Discussion The present results confirm and extend earlier studies indicating that underfeeding resulted in reduced anterior pituitary function (1-10). Few of the previous investigations included assays of hormone levels in the blood, since RIAs for pituitary hormones were not available. The present study strongly indicates that the major effects of inanition are exerted on the hypothalamus rather than on the pituitary, since the responsiveness of the pituitary of underfed rats to stimulation by LHRH + TRH remained the same or was even greater than the pituitary of ad libitum-fed rats. The reduction in secretion of AP hormones as a result of restricted food intake therefore appears to be due primarily to a decrease in release of hypothalamic hormones that control AP function. Previous reports from our laboratory indicate that concentrations of hypothalamic factors are reduced by chronic inanition in the rat (14,17-19), although a recent report (26) suggests that AS does not decrease hypothalamic LHRH. If hypothalamic hormone content is decreased by CS, this together with the present evidence for diminished release suggests that the synthesis of hypothalamic hormones is decreased by long-term starvation. The 5 AP hormones did not all respond the same to restricted feeding. The decreases in serum LH and TSH were greater than for FSH, PRL and GH, suggesting that the mechanism controlling release of LH and TSH may be more sensitive to the effects of inanition than for the other 3 hormones. The fact that the hormone levels reached stable low levels in AS rats and did not fall further during 14 days of lA ad libitum intake also suggests that the hypothalamus is affected before the body weight and organ weights equilibrate to the new low plane of nutrition. Upon refeeding for 7 days after

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586

CAMPBELL ET AL.

7 days of starvation and 14 days of inanition, serum LH and FSH rose to levels about 2V2 times greater than present in ad libitumfed controls. This remarkable capacity of the 2 gonadotropins to rebound from the effects of inanition may be due in part to increased release of LHRH. There was no indication that the 2 gonadotropins were more responsive to LHRH stimulation in the refed rats than in the ad libitum-fed controls. In fact, judged on the basis of change in release relative to pre-LHRH injection levels, the responsiveness of LH to LHRH in R rats was less than normal. There was no significant FSH response by R rats to the amount of LHRH used in this experiment. Serum TSH levels were only about xh of the ad libitum-fed control values after refeeding for 7 days. The TSH response to TRH, relative to pre-injection levels was similar to that found in fully-fed rats, but the absolute response was only about Vi normal. It is not known why the AP responsiveness was diminished by refeeding, nor why this condition co-exists, on the one hand, with high circulating levels of hormones (LH and FSH), and on the other, with low levels (TSH). It is possible that massive release of LHRH and TRH, during refeeding, eventually lead to a decrease in the number of free AP receptors for releasing-hormones. This reduction might then be reflected in< a lower response to administered releasing-hormones, independently of the unstimulated rate of secretion. Furthermore, decrements in AP hormone storage probably accompany high secretion rates during refeeding and this could further restrict hormone elevation following releasing-hormone administration, and could eventually lead to decreased circulating hormone levels, as in the case of TSH in R rats. The fall in serum PRL and GH during underfeeding in the present study is in agreement with previous reports from our laboratory that inanition resulted in reduced pituitary content of PRL (9) and in decreased pituitary and blood GH levels as indicated by bioassays of these hormones (17). The decline in serum GH during starva-

Endo • 1977 Vol 100 • No 2

tion in the rat is in marked contrast to the rise in blood GH levels observed in human subjects (27), and may represent yet another instance of the differences in GH release in response to similar stimuli reported in these 2 species (28). In the present study, the changes in food intake were believed to be of sufficient duration that alterations in hormone levels could be considered to reflect fairly changes in AP hormone secretion. Accordingly, the marked rise in circulating levels of TSH, LH, FSH, and PRL in response to LHRH + TRH administration during food restriction suggests that the pituitaries of these rats responded as well or even better than the pituitaries of ad libitum-fed rats. The fall in GH observed in all groups after LHRH + TRH administration is of interest and the explanation for this is not entirely clear. However, it is possible that the stress of repeated bleeding produced the decrease in serum GH since stress in rats has been reported to depress GH release (29). The smallest decrease in GH were observed in CS rats, suggesting that these rats were less reactive to stressful stimuli. It is not known why PRL only rose during AS, but this may reflect enhancement of AP sensitivity by the more stressful nature of AS as opposed to all of the other regimens. The conclusions that the AP of starved rats responded as well or better than normal to provocation by releasing hormones appear to run contrary to that derived from several recent clinical investigations. Thus, Warren et al. (31) and Sherman et al. (32) reported that the integrated LH response to LHRH administration was absent or strikingly impaired in women with anorexia nervosa of severity sufficient to cause more than 25% loss of body weight. Vinik et al. (33) reported a blunted response to TRH administration in humans fasted for 36 h. However, since integrated values for the amount of hormones released, or for the absolute value for hormone concentration after treatment, were not considered in relation to prior levels of hormone secretion in these clinical studies, their analysis of

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STARVATION EFFECTS ON AP HORMONES the data is not strictly comparable with that reported here. When judged on the same basis as ours, their results appear to be in essential agreement with ours. At the same time, there may be species and other differences in the response of underfed humans and rats to stimulation by hypothalamic hormones. Rootetal. (34) concluded that the AP of adult male rats without food for 7 days retained its sensitivity to synthetic LHRH in vivo under urethane anesthesia, in agreement with our results. They also tested the response of the AP in vitro and found normal LH and FSH release in the presence of LHRH. The decreases in organ weights observed in this investigation are in general agreement with earlier reports of the marked influence of inanition on target organ weights (1,4,10). The small reduction in testicular weight presumably reflects the relative insensitivity of this organ to inanition. The reduction in seminal fluid during starvation was overcome by refeeding, as was the weight loss of the prostate. These latter organs appeared to suffer atrophy so long as starvation continued despite the fact that hormone levels stabilized after 7 days starvation, indicating that the low circulating level of LH was not sufficient to maintain adequate steroidogenesis for their support. The increment in adrenal weight observed 7 days after food removal was reported previously (9), and presumably reflects the stressful nature of acute starvation. However, partial feeding for 2 weeks resulted in a significant but small reduction in absolute adrenal weight, also in agreement with earlier reports (9). References 1. Mulinos, M. C , L. Pomerantz, J. Smelser, and R. Kurzrok, Proc Soc Exp Biol Med 40: 79, 1939. 2. Werner, S., Proc Soc Exp Biol Med 41: 101, 1939. 3. Stephens, D. J., and W. M. Allen, Endocrinology 28: 580, 1941. 4. Klinefelter, H. F., Jr., F. Albright, and G. C. Grisw o l d j Clin Endocrinol 3: 529, 1943. 5. Maddock, W. O., and C. G. Heller, Proc Soc Exp Biol Med 66: 595, 1947.

587

6. Rinaldini, L.M.J Endocrinol 6: 54, 1949. 7. Zubiran, S., and F. Gomez-Mont, Vitam Horm 11: 97, 1953. 8. Perloff, W. H., E. M. Lasche, J. H. Nodine, N. G. Schneeberg, and C. B. Vieillard, JAMA 155: 1307, 1954. 9. Meites, J., and J. O. Reed, Proc Soc Exp Biol Med 70: 513, 1949. 10. Marrian, G. F., and A. S. Parkes, Proc R Soc, Ser B, Biol Sci 105: 248, 1929. 11. Srebnik, H. H., and M. M. Nelson, Proc Sixth Inter Confr Nutr Edinburgh, 375, 1963. 12. D'Angelo, S. A., Endocrinology 48: 341, 1951. 13. Meites, J., and L. F. Wolterink, Science 111: 175, 1950. 14. Meites, J., and N. J. Fiel, Endocrinology 77: 455, 1965. 15. Trenkel, A., Proc Soc Exp Biol Med 135: 77, 1970. 16. Leathern, J. H., Recent Prog Horm Res 14: 141, 1958. 17. Dickerman, E., A. Negro-Vilar, and J. Meites, Endocrinology 84: 814, 1969. 18. Piacsek, B. E., and J. Meites, Endocrinology 81: 535, 1967. 19. Negro-Vilar, A., E. Dickerman, and J. Meites, Endocrinology 88: 1246, 1971. 20. Ibrahim, E. A., and B. E. Howland, Can J Physiol Pharmacol 50: 768, 1972. 21. Root, A. W., and R. D. Russ, Ada Endocrinol (Kbh) 70: 665, 1972. 22. Assenmacher, I., A. Tixier-Vidal, and H. Astier, Ann Endocrinol 26: 1, 1965. 23. Niswender, G. D., C. L. Chen, A. R. Midgley, Jr., J. Meites, and S. Ellis, Proc Soc Exp Biol Med 130: 793, 1969. 24. Niswender, G. D., A. R. Midgley, Jr., S. E. Monroe, and L. E. Reichert, Proc Soc Exp Biol Med 128: 807, 1968. 25. Sokal, R. R ., and F. J. Rohlf, Biometry, W. H. Freeman, San Francisco, 1969. 26. Root, A. W., E. O. Reiter, G. E. Duckett, and M. L. Sweetland, Proc Soc Exp Biol Med 150: 602,1975. 27. Glick, S. M., J. Roth, R. S. Yalow, and S. A. Berson, Recent Prog Horm Res 21: 241, 1965. 28. Reichlin, S., In Greep, R. O., and E. B. Astwood (eds.), Handbook of Physiology, section 7, vol. 4, part 2, Waverly Press, Baltimore, 1974, p. 405. 29. Takahashi, Y., D. M. Kipnis, and W. H. Daughaday, Endocrinology 88: 909, 1971. 30. Warren, M. P., R. Jewelewicz, R. Dyrenfurth, I. Ans., R. Khalaj, and R. VandeWieleJ Clin Endocrinol Metab 40: 601, 1975. 31. Sherman, B. W., K. A. Halmi, and R. Zamudio, J Clin Endocrinol Metab 41: 135, 1975. 32. Vinik, A. I., W. J. Kalk, H. McLaren, S. Hendricks, and B. L. Pimstone, J Clin Endocrinol Metab 40: 509, 1975. 33. Root, A. W., and G. E. Duckett, Proc Soc Exp Biol Med 144: 30, 1973.

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Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolactin; response to LH-releasing hormone and thyrotropin-releasing hormone.

Effects of Starvation in Rats on Serum Levels of Follicle Stimulating Hormone, Luteinizing Hormone, Thyrotropin, Growth Hormone and Prolactin; Respons...
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