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Elevated plasma luteinizing hormone concentrations, cryptorchidism and mania
Psychoneuroendocrinology,Vol. 12, No. I, pp. 73--77, 1987. Printed in Great Britain.
0306 - 4530/87 $3.00 + 0.00 PergamonJournalsLtd.
CASE
REPORT
ELEVATED PLASMA LUTEINIZING HORMONE CONCENTRATIONS, CRYPTORCHIDISM AND MANIA L. J. WHALLEY, J. E. CHRISTIE, J. BENNIE, H. DICK, J. SLOAN-MURPHYAND G. FINK Medical Research Council, Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, Scotland, U.K.
(Received 21 August 1985; in f i n a I J o r m 7 October 1985) SUMMARY A young man 'with acute mania and unilateral cryptorchidism had plasma luteinizing hormone (LH) concentrations that were much higher than the maximum LH concentrations we have found in normal subjects and patients with schizophrenia. Plasma concentrations of testosterone and sex hormone binding globulin were not abnormal, showing that the elevated plasma LH concentrations were probably due to increased secretion of LH-releasing hormone (LHRH). This case supports our previous results which suggest that an abnormally high secretion of LHRH, due presumably to an abnormality in central neurotransmission, may be a feature of acute mania in young men. INTRODUCTION
WE PREVIOUSLY reported that the plasma concentrations of luteinizing hormone (LH) are significantly increased in young men with mania compared with the plasma concentrations of LH in men with schizophrenia or in normal subjects (Whalley et al., 1985). The study identified one young man (not included in the analysis) with acute, firstonset mania and a history of orchidopexy at age 12 years to correct bilateral cryptorchidism. We now report the case o f a second young man with a history of unilateral cryptorchidism who suffered a manic relapse of an otherwise typical recurrent manic-depressive illness, and in w h o m it was possible to relate changes in the plasma concentrations of LH to changes in the severity of his manic illness. We suggest that this may not be a chance association between mania and cryptorchidism and may be o f relevance to the putative abnormalities o f central neurotransmission in mania. CASE REPORT A 23-year-old man from Pakistan with unilateral cryptorchidism suffered a severe manic relapse of an established manic-depressive disorder. On hospital admission he weighed 57 kg, was 167 cm high, and had a normal beard growth and distribution of axillary and pubic hair. No testis could be found on the left side, but the right testis was of normal size and completely descended. During his stay in hospital his behaviour was frequently sexually aggressive. He had been free of medication for more than one year, but may have received chlorpromazine (300 mg orally) two days before admission. Blood samples were taken at 0800 h a n d / o r 0830 h on eight different days during his first two weeks in hospital, and the plasma concentrations of LH, follicle stimulating hormone (FSH), prolactin (PRL), testosterone, and sex hormone binding globulin (SHBG) were determined as described previously (Whalley et al+, 1985). Changes in clinical severity were rated on the manic rating scale (Biegel et al., 1971), and a diagnosis of mania was based upon the Research Diagnostic Criteria of Spitzer et al. (1978), following the clinical history and data from an interview between [he patien! and a native Urdu-speaking medical student. [+igure 1 shows that plasma LH concentrations varied during the study period: LH increased during the first two weeks in hospital and then fell at a time when the patient's clinical state improved. Through the study, his plasma l.H concentrations were always well above the upper limit reported for healthy young men (3.0 IU/I. 73
74
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, FSH
LH
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LITHIUM
manic rating /
,
~ HU~PROMAZ
\
/
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,
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[l"s 1 . 0 - i0.$
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• ), follicle stimulating hormone (FSH, FIo. l. Plasma concentrations of luteinizing hormone (LH • L_Ir_]), and prolactin (PRL ) in a 23-year-old man with mania and unilateral cryptorchidism during his first 16 days in hospital. Changes in the severity of manic symptoms ( • - - - • ) correspond to the vertical scale of the figure. Medication is shown by horizontal bars at the top of figure: daily doses, chlorpromazine 800 rag (day IO- 13), 1200 nag (day 14 - 16); lithium carbonate 2000 mg (day 3), 2400 nag (day 4 - 6), 1600 mg (day 6 - 16); amylobarbitone 400 mg (day 1), 800 mg (day 2), 500 nag (day 3), 200 mg (day 4), 600 mg (day 5 - 8 ) , 400 mg (day 9), 600 mg (day 10), 400 mg (day 11 - 12), 200 mg (day 1 3 - 16). mean 2.2, S.D. 0.5 IU/I; Whalley er al., 1985), young men with a history of unilateral cryptorchidism and compensatory testicular hypertrophy (3.6 IU/I, mean 2.3, S.D. 0.8 IU/I; Laron et al., 1980), and drug-free young men with mania ( 1.7 - 5.8 IU/I, mean 3.3, S.D. 1.1 IU/1; Whalley et al., 1985). Before the introduction of neuroleptic medication, his plasma PRL concentrations also were higher than expected, perhaps related to apreadmission dose of chlorpromazine. After the introduction of chlorpromazine, plasma PRL began to increase, as expected from many previous studies (e.g. Kolakowska et al., 1975; Meitzer & Fang, 1976). The plasma FSH concentrations (Fig. 1) were within the normal range (2.4 - 8.8 IU/I; Whalley et al., 1985), as were the patient's plasma concentrations of testosterone (14.1 - 19.0 nmoi/l and SHBG (16.8- 34.1 nmol/l). Because the plasma LH concentrations were much greater than those reported for other endocrinolmthies in men, we determined the nature of the plasma LH immunoreactivity using gel filtration. Figure 2 shows that the plasma LH coeluted with purified LH standard. Therefore, the high plasma LH concentrations in this patient were due to authentic immunoreactive LH. The patient recovered slowly from the manic phase of his illness and was eventually discharged from hoslmtal. In spite of adequate lithium prophylaxis, he suffered two further episodes of mania before returning to Pakistan, where he married and fathered a child. DISCUSSION
These data provide further evidence that acute mania in young men can be associated
with a selective increase in plasma LH concentration, rncreased plasma EH concentration could result from a failure in negative feedback, an increase in the responsiveness o f the anterior pituitary gland to LH-reteasing hormone (LHRH), and/or an increased release of LHRH into the hypophysial portal vessels. Failure in negative feedback can be ruled out in this patient, since his plasma concentrations of testosterone and SHBG were within the normal range. In the presence of normal plasma testosterone concentrations, increased
CR','PTORCI-IIDISM, LH AND MANIA
75
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-40
7 6
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5
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35 45 No of fractions
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hc,. 2. Gel filtration studies on plasma from a 23-year-old man with unilateral cryptorchidism and mania. One ml of plasma was applied to a 900 × 15 mm Sephadex G 150 column, and fractions of 2.5 ml were collected. The arrow indicates the void volume, the line ( • • ) shows the position of free '251, and the line ( • -- • ) is the position o f ' " q l L H (iodination grade). The patient's plasma ([ j [ I) eluted at the same position as '~1 LH, indicating that the plasma contained authentic immunoreactive LH.
pituitary responsiveness to L H R H , if it occurred, is likely to be due to the priming effect of L H R H brought about by increased release of L H R H (Aiyer et al., 1974; Fink & Henderson, 1977; Fink, 1979), a mechanism which has been invoked previously to explain the positive correlation between basal concentrations of plasma LH and the LH response to L H R H in man (e.g. Roth et al., 1972; Aiyer et al., 1974). Therefore, the present data, together with our previous data (Whalley et al., 1985), suggest that the abnormally high plasma L H concentrations in manic men are due to an increased release of L H R H . Increased release of L H R H may reflect an abnormality in the central neurotransmitter systems, such as the monoaminergic and opioid systems, that modulate L H R H release (Barraclough & Wise, 1982; Kalra & Kalra, 1983; Whalley et al., 1985). In our previous report, we noted that plasma LH concentrations fell on recovery from the manic phase of illness in three out of five patients studied. The present case provides further evidence that plasma LH is increased in mania and falls on recovery, but not necessarily to within the normal range. In contrast to the LH concentrations, which at certain times were more than six-fold greater than the maximum concentrations in normal subjects (Whalley et al., 1985), plasma FSH concentrations did not exceed the normal limit. This supports our previous finding of an apparent dissociation between the secretion of FSH and LH in patients with mania. Dissociation between LH and FSH secretion is known to occur under several physiological and experimental conditions, but the precise explanation for the dissociation remains unknown (e.g. Fink, 1979; Lumpkin & McCann, 1984). In the
76
!.
i \~1t\111'~ ~'[dt
present case, as well as in the patients studied by Whalley el al. (1985), the most tikel\ explatmtions for abnormally raised LH but not FSH concentrations are that the I.SH response to LHRH may have been moderated by inhibin secreted by the testes (Robertson el al., 1985), or that secretion of the proposed specific FSH-releasing ractor (t.umpkin & McCann, 1984) is not abnormal in manic patients. The reason for the normal plasma concentrations of testosterone in the presence or markedly elevated concentrations of LH is not clear, but phenothiazines have been shown to reduce plasma concentrations of testosterone without changing plasma LH concentrations ~Beumont et al., 1974); conceivably, the inhibitory effects of neurolepttcs on testosterone secretion tn the present patient may have counteracted the stimulatory effects of the high plasma LH concentrations. The present and previous (Whalley et al.. 1985) studies also suggest that there ma~, be an association between cryptorchidism and mania. So far, 14 male patients with mania selected from routine referrals to the Royal Edinburgh Hospital have entered our neuroendocrine study programme. A history of cryptorchidism was given by two patients (14%). It is important to establish whether this is due to chance or whether cryptorchidism is associated with manic-depressive illness, since only 0.7% of the male population has a history of cryptorchidism (Scorer, 1964; Whitaker, 1970). Further studies on the prevalence of testicular pathology in manic-depressive illness and the psychological sequelae of cryptorchidism are therefore warranted. We thank Norma Brearley and Jo Donnelly for the preparation of this manuscript, the nursing staff of the Metabolic Unit for their invaluable assistance, and the National H o r m o n e and Pituitary Program o f the N1ADDK, Baltimore, MD., U . S . A . , for the generous supply of radioimmunoassay materials. REFERENCES
Aiyer M S, C h i a p p a S A, Fink G (1974) A priming effect of luteinizing hormone releasing factor on the anterior pituitary gland in the female rat..I Endocrinol 6 2 : 5 7 3 -- 588. Barraclough C, Wise P M (19821 The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion, Lndocr Rev 3: 9t - 119. Beumont P J V, Corker C S. Friesen H G, Kolakowska T, Mandetbrote B M, Marshall J, Murray M A F, Wiles D H (19741 The effects of phenothiazenes on endocrine function: II Effects m men and post-menopausal women. Br J Psychiatry 124:420 - 430. Biegel A, Murphy D L, Bunney W E (1971) The Manic State Rating Scale. Arch Gen Psychiatry25: 2 5 6 - 262. Fink G 0 9 7 9 ) Feedback actions of target hormones on hypothalamus and pituitary with special reference to gonadal steroids. Ann Rev Physiol 41:571 585 Fink G, Henderson S R (1977) Steroids and pituitary responsiveness ill female, androgenized female and male rats. J Endocrinol 73:157 - 164. Kalra S P, Kalra P S (1983) Neural regulation of hueinizing hormone secretion in the rat. Endocr Rev 4: 311
351.
Kolakowska T, Wiles D H, McNeitly A S, Gelder M (1975) Correlation between plasma levels of chlorpromazine and prolactin in psychiatric patients. Psychol Med 5: 2 1 4 - 2 1 6 . Laron Z, Dickerman Z, Ritterman I, Kaufman H (1980) Follow-up of boys with unilateral compensatory testicular hypertrophy. Fertil Steril 33:297 - 301. Lumpkin M H, McCann S M (1984) Effect of destruction of the dorsal anterior hypothalamus on folliclestimulating hormone secretion in the rat. Endocrinology 115:2473 - 3480. Meltzer H Y, Fang V S (1976) The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry 3 3 : 2 7 9 - 286.
CRYPTORCHIDISM,LH AND MANI*'~
77
Robertson D M, Foulds L M, Leverska L, Morgan F, J, Hearn M T W, Burger H G, Wettenhall R E H, de Kretser D M (1985) Isolation of inhibin from bovine follicular fluid. Biochem Biophys Res C o m m u n 226: 220 - 226. Roth J C, Kelch R P, Kaplan S L, G r u m b a c h M M (1972) FSH and LH response to luteinizing hormone releasing factor in prepubertal and pubertal children, adult males and patients with hypogonadotropic and hypergonadotropic hypogonadism. J Clin Endocrinol Metab 35: 9 2 6 - 930. Scorer G (1964) The descent of the testis. Arch Dis Child 39:605 - 6 0 9 . Spitzer R, Endicott J, Robins E (1978) Research Diagnostic Criteria: rationale and reliability. Arch Gen Psychiatry 35:773 - 782. ~ h a l l e y L J. Christie J E , Bennie J, Dick H, Blackburn I M, Blackv, ood D, Sanchez Watts G, Fink G (1985) Selective increase in plasma luteinising hormone concentrations in drug free young men with mania. B r M e d J 2911: 9 9 - 102. "~'hitaker R H (1970) Management of the undescended testis. Br .I Iqosp Med 14:25 37.
0306 - 4530/87 $3.00 + 0.00 PergamonJournalsLtd.
CASE
REPORT
ELEVATED PLASMA LUTEINIZING HORMONE CONCENTRATIONS, CRYPTORCHIDISM AND MANIA L. J. WHALLEY, J. E. CHRISTIE, J. BENNIE, H. DICK, J. SLOAN-MURPHYAND G. FINK Medical Research Council, Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, Scotland, U.K.
(Received 21 August 1985; in f i n a I J o r m 7 October 1985) SUMMARY A young man 'with acute mania and unilateral cryptorchidism had plasma luteinizing hormone (LH) concentrations that were much higher than the maximum LH concentrations we have found in normal subjects and patients with schizophrenia. Plasma concentrations of testosterone and sex hormone binding globulin were not abnormal, showing that the elevated plasma LH concentrations were probably due to increased secretion of LH-releasing hormone (LHRH). This case supports our previous results which suggest that an abnormally high secretion of LHRH, due presumably to an abnormality in central neurotransmission, may be a feature of acute mania in young men. INTRODUCTION
WE PREVIOUSLY reported that the plasma concentrations of luteinizing hormone (LH) are significantly increased in young men with mania compared with the plasma concentrations of LH in men with schizophrenia or in normal subjects (Whalley et al., 1985). The study identified one young man (not included in the analysis) with acute, firstonset mania and a history of orchidopexy at age 12 years to correct bilateral cryptorchidism. We now report the case o f a second young man with a history of unilateral cryptorchidism who suffered a manic relapse of an otherwise typical recurrent manic-depressive illness, and in w h o m it was possible to relate changes in the plasma concentrations of LH to changes in the severity of his manic illness. We suggest that this may not be a chance association between mania and cryptorchidism and may be o f relevance to the putative abnormalities o f central neurotransmission in mania. CASE REPORT A 23-year-old man from Pakistan with unilateral cryptorchidism suffered a severe manic relapse of an established manic-depressive disorder. On hospital admission he weighed 57 kg, was 167 cm high, and had a normal beard growth and distribution of axillary and pubic hair. No testis could be found on the left side, but the right testis was of normal size and completely descended. During his stay in hospital his behaviour was frequently sexually aggressive. He had been free of medication for more than one year, but may have received chlorpromazine (300 mg orally) two days before admission. Blood samples were taken at 0800 h a n d / o r 0830 h on eight different days during his first two weeks in hospital, and the plasma concentrations of LH, follicle stimulating hormone (FSH), prolactin (PRL), testosterone, and sex hormone binding globulin (SHBG) were determined as described previously (Whalley et al+, 1985). Changes in clinical severity were rated on the manic rating scale (Biegel et al., 1971), and a diagnosis of mania was based upon the Research Diagnostic Criteria of Spitzer et al. (1978), following the clinical history and data from an interview between [he patien! and a native Urdu-speaking medical student. [+igure 1 shows that plasma LH concentrations varied during the study period: LH increased during the first two weeks in hospital and then fell at a time when the patient's clinical state improved. Through the study, his plasma l.H concentrations were always well above the upper limit reported for healthy young men (3.0 IU/I. 73
74
I . I. \~,}i,\ill~
t_q
l__.r-- ]
AmVtonA.alrO.E
, FSH
LH
8-2
25,
..a 6.5 20
el~d.
LITHIUM
manic rating /
,
~ HU~PROMAZ
\
/
",,/
Z
(!/
~4"9 15 Z -i it
,t 3-2
10.
|
.....,,
,
•y
, i
o.
1-8
5-
o°..o.."
[l"s 1 . 0 - i0.$
0-
Day
• ), follicle stimulating hormone (FSH, FIo. l. Plasma concentrations of luteinizing hormone (LH • L_Ir_]), and prolactin (PRL ) in a 23-year-old man with mania and unilateral cryptorchidism during his first 16 days in hospital. Changes in the severity of manic symptoms ( • - - - • ) correspond to the vertical scale of the figure. Medication is shown by horizontal bars at the top of figure: daily doses, chlorpromazine 800 rag (day IO- 13), 1200 nag (day 14 - 16); lithium carbonate 2000 mg (day 3), 2400 nag (day 4 - 6), 1600 mg (day 6 - 16); amylobarbitone 400 mg (day 1), 800 mg (day 2), 500 nag (day 3), 200 mg (day 4), 600 mg (day 5 - 8 ) , 400 mg (day 9), 600 mg (day 10), 400 mg (day 11 - 12), 200 mg (day 1 3 - 16). mean 2.2, S.D. 0.5 IU/I; Whalley er al., 1985), young men with a history of unilateral cryptorchidism and compensatory testicular hypertrophy (3.6 IU/I, mean 2.3, S.D. 0.8 IU/I; Laron et al., 1980), and drug-free young men with mania ( 1.7 - 5.8 IU/I, mean 3.3, S.D. 1.1 IU/1; Whalley et al., 1985). Before the introduction of neuroleptic medication, his plasma PRL concentrations also were higher than expected, perhaps related to apreadmission dose of chlorpromazine. After the introduction of chlorpromazine, plasma PRL began to increase, as expected from many previous studies (e.g. Kolakowska et al., 1975; Meitzer & Fang, 1976). The plasma FSH concentrations (Fig. 1) were within the normal range (2.4 - 8.8 IU/I; Whalley et al., 1985), as were the patient's plasma concentrations of testosterone (14.1 - 19.0 nmoi/l and SHBG (16.8- 34.1 nmol/l). Because the plasma LH concentrations were much greater than those reported for other endocrinolmthies in men, we determined the nature of the plasma LH immunoreactivity using gel filtration. Figure 2 shows that the plasma LH coeluted with purified LH standard. Therefore, the high plasma LH concentrations in this patient were due to authentic immunoreactive LH. The patient recovered slowly from the manic phase of his illness and was eventually discharged from hoslmtal. In spite of adequate lithium prophylaxis, he suffered two further episodes of mania before returning to Pakistan, where he married and fathered a child. DISCUSSION
These data provide further evidence that acute mania in young men can be associated
with a selective increase in plasma LH concentration, rncreased plasma EH concentration could result from a failure in negative feedback, an increase in the responsiveness o f the anterior pituitary gland to LH-reteasing hormone (LHRH), and/or an increased release of LHRH into the hypophysial portal vessels. Failure in negative feedback can be ruled out in this patient, since his plasma concentrations of testosterone and SHBG were within the normal range. In the presence of normal plasma testosterone concentrations, increased
CR','PTORCI-IIDISM, LH AND MANIA
75
8-
-40
7 6
3b
i
5
25
tO
4
E
3
t-
2-
O ~J
1
2O
*6
t-
10 sensitivity threshold
..../ ~, ~ ' - ' 7 ,
1'5
2'5
.
35 45 No of fractions
"-. ,
,
55
5
t .~"""r-
65
:
:
.....
75
.
%
8s
hc,. 2. Gel filtration studies on plasma from a 23-year-old man with unilateral cryptorchidism and mania. One ml of plasma was applied to a 900 × 15 mm Sephadex G 150 column, and fractions of 2.5 ml were collected. The arrow indicates the void volume, the line ( • • ) shows the position of free '251, and the line ( • -- • ) is the position o f ' " q l L H (iodination grade). The patient's plasma ([ j [ I) eluted at the same position as '~1 LH, indicating that the plasma contained authentic immunoreactive LH.
pituitary responsiveness to L H R H , if it occurred, is likely to be due to the priming effect of L H R H brought about by increased release of L H R H (Aiyer et al., 1974; Fink & Henderson, 1977; Fink, 1979), a mechanism which has been invoked previously to explain the positive correlation between basal concentrations of plasma LH and the LH response to L H R H in man (e.g. Roth et al., 1972; Aiyer et al., 1974). Therefore, the present data, together with our previous data (Whalley et al., 1985), suggest that the abnormally high plasma L H concentrations in manic men are due to an increased release of L H R H . Increased release of L H R H may reflect an abnormality in the central neurotransmitter systems, such as the monoaminergic and opioid systems, that modulate L H R H release (Barraclough & Wise, 1982; Kalra & Kalra, 1983; Whalley et al., 1985). In our previous report, we noted that plasma LH concentrations fell on recovery from the manic phase of illness in three out of five patients studied. The present case provides further evidence that plasma LH is increased in mania and falls on recovery, but not necessarily to within the normal range. In contrast to the LH concentrations, which at certain times were more than six-fold greater than the maximum concentrations in normal subjects (Whalley et al., 1985), plasma FSH concentrations did not exceed the normal limit. This supports our previous finding of an apparent dissociation between the secretion of FSH and LH in patients with mania. Dissociation between LH and FSH secretion is known to occur under several physiological and experimental conditions, but the precise explanation for the dissociation remains unknown (e.g. Fink, 1979; Lumpkin & McCann, 1984). In the
76
!.
i \~1t\111'~ ~'[dt
present case, as well as in the patients studied by Whalley el al. (1985), the most tikel\ explatmtions for abnormally raised LH but not FSH concentrations are that the I.SH response to LHRH may have been moderated by inhibin secreted by the testes (Robertson el al., 1985), or that secretion of the proposed specific FSH-releasing ractor (t.umpkin & McCann, 1984) is not abnormal in manic patients. The reason for the normal plasma concentrations of testosterone in the presence or markedly elevated concentrations of LH is not clear, but phenothiazines have been shown to reduce plasma concentrations of testosterone without changing plasma LH concentrations ~Beumont et al., 1974); conceivably, the inhibitory effects of neurolepttcs on testosterone secretion tn the present patient may have counteracted the stimulatory effects of the high plasma LH concentrations. The present and previous (Whalley et al.. 1985) studies also suggest that there ma~, be an association between cryptorchidism and mania. So far, 14 male patients with mania selected from routine referrals to the Royal Edinburgh Hospital have entered our neuroendocrine study programme. A history of cryptorchidism was given by two patients (14%). It is important to establish whether this is due to chance or whether cryptorchidism is associated with manic-depressive illness, since only 0.7% of the male population has a history of cryptorchidism (Scorer, 1964; Whitaker, 1970). Further studies on the prevalence of testicular pathology in manic-depressive illness and the psychological sequelae of cryptorchidism are therefore warranted. We thank Norma Brearley and Jo Donnelly for the preparation of this manuscript, the nursing staff of the Metabolic Unit for their invaluable assistance, and the National H o r m o n e and Pituitary Program o f the N1ADDK, Baltimore, MD., U . S . A . , for the generous supply of radioimmunoassay materials. REFERENCES
Aiyer M S, C h i a p p a S A, Fink G (1974) A priming effect of luteinizing hormone releasing factor on the anterior pituitary gland in the female rat..I Endocrinol 6 2 : 5 7 3 -- 588. Barraclough C, Wise P M (19821 The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion, Lndocr Rev 3: 9t - 119. Beumont P J V, Corker C S. Friesen H G, Kolakowska T, Mandetbrote B M, Marshall J, Murray M A F, Wiles D H (19741 The effects of phenothiazenes on endocrine function: II Effects m men and post-menopausal women. Br J Psychiatry 124:420 - 430. Biegel A, Murphy D L, Bunney W E (1971) The Manic State Rating Scale. Arch Gen Psychiatry25: 2 5 6 - 262. Fink G 0 9 7 9 ) Feedback actions of target hormones on hypothalamus and pituitary with special reference to gonadal steroids. Ann Rev Physiol 41:571 585 Fink G, Henderson S R (1977) Steroids and pituitary responsiveness ill female, androgenized female and male rats. J Endocrinol 73:157 - 164. Kalra S P, Kalra P S (1983) Neural regulation of hueinizing hormone secretion in the rat. Endocr Rev 4: 311
351.
Kolakowska T, Wiles D H, McNeitly A S, Gelder M (1975) Correlation between plasma levels of chlorpromazine and prolactin in psychiatric patients. Psychol Med 5: 2 1 4 - 2 1 6 . Laron Z, Dickerman Z, Ritterman I, Kaufman H (1980) Follow-up of boys with unilateral compensatory testicular hypertrophy. Fertil Steril 33:297 - 301. Lumpkin M H, McCann S M (1984) Effect of destruction of the dorsal anterior hypothalamus on folliclestimulating hormone secretion in the rat. Endocrinology 115:2473 - 3480. Meltzer H Y, Fang V S (1976) The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry 3 3 : 2 7 9 - 286.
CRYPTORCHIDISM,LH AND MANI*'~
77
Robertson D M, Foulds L M, Leverska L, Morgan F, J, Hearn M T W, Burger H G, Wettenhall R E H, de Kretser D M (1985) Isolation of inhibin from bovine follicular fluid. Biochem Biophys Res C o m m u n 226: 220 - 226. Roth J C, Kelch R P, Kaplan S L, G r u m b a c h M M (1972) FSH and LH response to luteinizing hormone releasing factor in prepubertal and pubertal children, adult males and patients with hypogonadotropic and hypergonadotropic hypogonadism. J Clin Endocrinol Metab 35: 9 2 6 - 930. Scorer G (1964) The descent of the testis. Arch Dis Child 39:605 - 6 0 9 . Spitzer R, Endicott J, Robins E (1978) Research Diagnostic Criteria: rationale and reliability. Arch Gen Psychiatry 35:773 - 782. ~ h a l l e y L J. Christie J E , Bennie J, Dick H, Blackburn I M, Blackv, ood D, Sanchez Watts G, Fink G (1985) Selective increase in plasma luteinising hormone concentrations in drug free young men with mania. B r M e d J 2911: 9 9 - 102. "~'hitaker R H (1970) Management of the undescended testis. Br .I Iqosp Med 14:25 37.