help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2005-0041
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Funabashi, T.
Right arrow Articles by Kimura, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Funabashi, T.
Right arrow Articles by Kimura, F.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Female Endocrinology
Right arrow Male Endocrinology
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 3908-3913
Copyright © 2005 by The Endocrine Society

Nicotine Inhibits Pulsatile Luteinizing Hormone Secretion in Human Males But Not in Human Females, and Tolerance to This Nicotine Effect Is Lost within One Week of Quitting Smoking

Toshiya Funabashi, Akane Sano, Dai Mitsushima and Fukuko Kimura

Department of Neuroendocrinology (T.F., A.K., D.M., F.K.), Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; and International University of Health and Welfare (F.K.), Tokyo 107-0062, Japan

Address all correspondence and requests for reprints to: Fukuko Kimura, M.D., Ph.D., Department of Neuroendocrinology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan. E-mail: fukuko{at}med.yokohama-cu.ac.jp.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context and Objective: Despite having increased knowledge of the adverse reproductive effects of smoking, it is unclear whether nicotine affects the pulsatile LH secretion in humans. We addressed this issue in male and female smokers and nonsmokers.

Subjects and Methods: Twenty-nine male and 16 female nonsmokers and smokers were recruited as volunteers. In male smokers, nicotine effect was also studied before and after quitting smoking. In females, cyclic ovulatory function was assessed by measuring basal body temperature, and sampling studies were performed during the follicular phase. In the morning of the sampling day, an iv catheter was inserted into an anterobrachial vein, and blood samples (1.0–1.5 ml each) were taken at 10-min intervals for 480 min, during which, at 240 min, nicotine was administered via a transdermal patch (Nicotinell transdermal therapeutic system) containing 17.5 mg nicotine. Plasma LH was measured by immunoradiometric assay kits.

Results: Nicotine significantly lengthened the interpulse interval of pulsatile LH secretion in male nonsmokers but not in female nonsmokers. In male smokers, nicotine did not lengthen the interpulse interval, and in female smokers it was also ineffective. After quitting cigarette smoking in male smokers, the refractory to nicotine effect disappeared within 1 wk.

Conclusions: We conclude that nicotine inhibits pulsatile LH secretion only in males, and the tolerance developed to the nicotine effect disappears within 1 wk of quitting cigarette smoking. However, we cannot deny the possibility that nicotine effect would have been detected in females if more subjects had been studied.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
IT HAS BEEN reported that sc injection of nicotine inhibits pulsatile LH secretion in ovariectomized rats (1). The site of this nicotine effect was assumed to be the medial basal hypothalamus because nicotine inhibited pulsatile LH secretion after partial or total deafferentation of the medial basal hypothalamus (1), but it did not inhibit GnRH-induced LH secretion in ovariectomized rats, ruling out its action on the anterior pituitary gland (1).

More recently we have shown that nicotine inhibits the activity of the GnRH pulse generator in ovariectomized rats (2). Nicotine inhibited multiunit activity in the median eminence region of the hypothalamus that expresses characteristic increases intermittently in association with LH pulses in ovariectomized rats (3). We found a similar inhibitory effect of nicotine on the pulsatile GnRH secretion in the cultured rat embryonic olfactory placode (4). This latter in vitro study suggested that the inhibitory effect of nicotine on the GnRH pulse generator is mediated by the {gamma}-aminobutyric acid (GABA)A receptor system.

Now we have focused our interest on the effect of nicotine on the pulsatile LH secretion in humans. The first aim of the present study (study 1) was to investigate whether nicotine administered via a transdermal patch [Nicotinell transdermal therapeutic system (TTS); Novartis Pharma, K. K., Tokyo, Japan] affects the pulsatile LH secretion in male and female nonsmokers. To the best of our knowledge, there has been one study that examined the nicotine effect on the pulsatile LH secretion in female nonsmokers (5) but none in male nonsmokers.

The second aim (study 2) was to determine how nicotine administered via transdermal patch affects the pulsatile LH secretion in male and female smokers. In this study we attempted to determine whether there was any change in the response to nicotine in comparison with that in nonsmokers. Although several reports have shown consistently, in male chronic smokers, an acute increasing influence of smoking on the secretion of GH (6, 7, 8, 9), prolactin (8, 10), and cortisol (ACTH) (6, 8, 9), either increasing influence (10) or no influence (6, 11) has been reported for LH.

After reaching the conclusion in study 2 that the pulsatile LH secretion in male chronic smokers was refractory to nicotine, we further attempted (study 3) to determine whether quitting smoking changes the response to nicotine in male smokers.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

A total of 29 male and 16 female Japanese nonsmokers and chronic smokers were recruited as volunteers for these studies. We obtained written informed consent for the study from all volunteers and the approval of the study from the institutional ethics committee of the Yokohama City University School of Medicine. Subjects were questioned about general conditions of their health, and on the day of blood sampling, their blood pressure and electrocardiogram were examined to exclude cardiovascular diseases.

All subjects were listed in Table 1Go with indications to which study they were assigned. Subjects in study 1 were 11 male and eight female volunteers who had no history of smoking (nonsmokers). Subjects in study 2 were 18 male and eight female volunteers who had smoked daily for more than 6 yr (smokers). Brinkmann Index, i.e. the number of cigarettes per day x years (12), was shown in Table 1Go. Subjects in study 3 were first assigned to study 2 and then to study 3 if they agreed to quit smoking. Six of nine males succeeded in quitting smoking at least for 1 month (Table 1Go). In female subjects, both nonsmokers and smokers, their cyclic ovulatory function was first assessed in a control cycle by measuring basal body temperature; they were all normally menstruating and have normal menstrual cycles (26–35 d in length). There was no difference in the length of the menstrual cycle between nonsmokers (30.8 ± 0.9 d) and smokers (29.6 ± 0.5 d). The first day of the cycle was dated from the day when menstruation began, and sampling studies were performed on d 5–10, i.e. during the follicular phase.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Summary of subjects

 
Procedures

All sampling studies were begun in the morning, between 0900 and 1000 h, in a quiet, temperature-controlled room. Subjects were permitted to take a breakfast 1 h before arriving but were instructed to consume, during the protocol, only blocks of a balanced food (Otsuka Pharmaceutical Co., Tokyo, Japan), each block containing 100 kcal for males and 50 kcal for females, at 60-min intervals and to drink green tea without sugar. This was to avoid a possible influence of changes in glucose level in blood caused by taking the meal (13).

An iv catheter (LELCO Plus, Johnson-Johnson, Brussels, Belgium) was inserted into an anterobrachial superficial vein in the nondominant arm. Blood samples (1.0–1.5 ml each) were taken through the catheter at 10-min intervals for a period of 480 min. After a 240-min control period, a Nicotinell TTS 10 (Novartis Pharma) containing 17.5 mg nicotine was attached to the abdominal skin and further blood samples were taken during another 240-min period (treatment period). Plasma samples were separated at room temperature and stored at –20 C.

Analytical methods and statistical analysis

Plasma LH was measured with immunoradiometric assay kits (Daiichi Radioisotope Institute, Tokyo, Japan), and a total of 18 assays were done. The intra- and interassay coefficients of variation (CVs) estimated at the mean LH level of 8.6 mIU/ml were 4.0 and 10.0%, respectively. Plasma total testosterone levels in the first sample were measured by a commercial RIA at Otsuka Assay Laboratories (Tokushima, Japan).

The LH pulse was identified using cluster analysis, a statistically based peak-detection algorithm (cluster 8) (14) with constant value of CV (8.5%). The parameters chosen were a nadir and peak size of 2 x 1 with a t statistic value of 2.6 for both increase and decrease. Because a last potential pulse during the 8-h blood sampling appeared to be not identified as a pulse by the cluster 8 program in many subjects, the last potential pulse was checked whether or not a LH pulse, using CV method (15, 16) in which a potential pulse was defined as an pulse when both the ascending and descending CVs were greater than 1.7 times the intraassay CV (15, 16). The CVs used for this pulse detection were 7.7–9.5%, depending on the assay CV.

The analysis of LH pulsatility included the determination of interpulse interval (the time between the two neighboring pulses) and the pulse amplitude (difference between the peak and the prepeak nadir). The interpulse interval and the pulse amplitude were averaged for both the control period and the treatment period. If a first pulse appeared within 90 min in males and 60 min in females during the treatment period, this pulse was defined as a pulse during the control period because the average interpulse interval during the control period was 90 min in males and 60 min in females (see Fig. 2Go).



View larger version (22K):
[in this window]
[in a new window]
  		FIG. 2. Effects of exposure to nicotine on the interpulse intervals of the pulsatile LH secretion. Each bar and vertical line indicate the mean and SE, respectively. Numbers in parentheses indicate the number of subjects. *, P < 0.05.

 
One-way ANOVA followed by Fisher’s protected least significant difference post hoc comparison or Student’s t test was used to test the statistical significance in each group, and significance was accepted at P < 0.05.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Effects of nicotine on pulsatile LH secretion in male and female nonsmokers (study 1)

In male nonsmokers, secretion of LH was apparently pulsatile. Interpulse intervals varied among subjects, but the mean interpulse interval was approximately 90 min during the control period (Figs. 1Go and 2Go). This was in good accord with previous reports (17, 18). As shown in Fig. 2Go, exposure to nicotine by attaching a Nicotinell TTS 10 significantly lengthened the interpulse interval (ANOVA, P < 0.05; post hoc, P < 0.05), suggesting that nicotine inhibits the GnRH pulse generator activity in the hypothalamus, followed by inhibition of the pulsatile LH secretion from the pituitary. Exposure to nicotine did not affect the pulse amplitude in male nonsmokers (Table 2Go, ANOVA, P > 0.1).



View larger version (24K):
[in this window]
[in a new window]
  		FIG. 1. Representative examples of effects of exposure to nicotine on the pulsatile LH secretion in male (left) nonsmokers and smokers, and female (right) nonsmokers and smokers. Nicotine was administered via a transdermal patch containing 17.5 mg nicotine (TTS 10). Shaded areas indicate the period of nicotine exposure. Numbers shown at the left upper position of each graph indicate the subject number. Triangles indicate statistically defined LH pulses.

 

View this table:
[in this window]
[in a new window]
  		TABLE 2. Amplitudes of LH pulses (mIU/ml)

 
In female nonsmokers, pulsatile LH secretion with an interpulse interval of approximately 60 min was evident during the control period (Figs. 1Go and 2Go). This interpulse interval in nonsmokers was in good accord with previous reports for the follicular phase (19, 20, 21). In contrast to male nonsmokers, exposure to nicotine affected neither the interpulse interval (Fig. 2Go, ANOVA, P > 0.1) nor the amplitude (Table 2Go, ANOVA, P > 0.1). These results indicated that female nonsmokers were refractory to nicotine, in contrast to male nonsmokers.

Effects of nicotine on pulsatile LH secretion in male and female smokers (study 2)

In male smokers, the LH secretory pattern was pulsatile and appeared to be similar to that in male nonsmokers during the control period (Fig. 1Go). There was no significant difference in the interpulse interval during the control period between male nonsmokers and male smokers. The interpulse interval in male smokers during the treatment period was also not significantly different from that during the control period (Fig. 2Go, ANOVA, P > 0.5), indicating that exposure to nicotine did not affect the pulsatile LH secretion in male smokers. The same was true for the pulse amplitude (Table 2Go, ANOVA, P > 0.1). The results indicated that tolerance to the inhibitory nicotine effect on pulsatile LH secretion had been developed in male smokers.

In female smokers, secretion of LH was pulsatile with an interpulse interval of approximately 60 min during the control period (Figs. 1Go and 2Go). This interpulse interval was not significantly different from that during the control period in female nonsmokers (Fig. 2Go, ANOVA, P > 0.5). Furthermore, as in nonsmokers, exposure to nicotine did not affect the interpulse interval in smokers; there was no significant difference in the interpulse interval between the control period and the treatment period (Fig. 2Go, ANOVA, P > 0.5). The same was true for the pulse amplitude (Table 2Go, ANOVA, P > 0.1).

Effects of nicotine on pulsatile LH secretion after quitting smoking in male smokers (study 3)

Representative profiles of the pulsatile LH secretion in smokers before and after quitting cigarette smoking are shown in Fig. 3Go. As already shown in study 2, exposure to nicotine did not have an inhibitory effect on the pulsatile LH secretion in male smokers, but this ineffectiveness of nicotine seemed to be lost after quitting smoking. Namely, at 1 wk and 1 month after quitting cigarette smoking, exposure to nicotine significantly lengthened the interpulse interval during the treatment period, compared with that during the control period (Fig. 4Go, ANOVA, P < 0.05; post hoc P < 0.05), without affecting the amplitude (Table 2Go, ANOVA, P > 0.1).



View larger version (32K):
[in this window]
[in a new window]
  		FIG. 3. Representative examples of effects of exposure to nicotine on the pulsatile LH secretion in male smokers before and 1 wk (1 W) and 1 month (1 M) after quitting smoking. For more details, see Fig. 1Go.

 


View larger version (29K):
[in this window]
[in a new window]
  		FIG. 4. Effects of exposure to nicotine on the interpulse intervals of the pulsatile LH secretion before and after quitting cigarette smoking in male smokers. For more details, see Figs. 2Go and 3Go.

 
Overall means of plasma concentrations of LH and testosterone in nonsmokers and smokers

To determine the influence of cigarette smoking on the LH secretion, overall means of serum LH concentrations were calculated for the control period in nonsmokers and smokers. As shown in Table 3Go, in males, mean plasma LH concentrations in smokers were significantly lower than in nonsmokers (Student’s t, P < 0.05), although there was no significant difference in plasma testosterone concentrations (Student’s t, P > 0.1) between nonsmokers (4.33 ± 0.53 ng/ml, n = 11) and smokers (4.84 ± 0.37 ng/ml, n = 18). In females, mean serum LH concentrations were not significantly different between nonsmokers and smokers (Student’s t, P > 0.1), in good accord with the ineffectiveness of nicotine on the parameter of pulsatile LH secretion.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Mean plasma LH concentrations during the control period

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Study 1 demonstrated for the first time that nicotine, which was administered via a transdermal patch, inhibits the pulsatile LH secretion in male nonsmokers. The interval of pulsatile LH secretion was significantly increased after the administration of nicotine, with no significant changes in the amplitude. It was reported that the plasma concentration of nicotine obtained 4 h after the administration of a transdermal patch containing 19 mg nicotine, which was most similar to the dose contained in Nicotinell TTS 10, was at most 5 ng/ml (22). This dose was much lower than about 40 ng/ml seen about 5 min after the single cigarette smoking (23) or about 23 ng/ml seen 14 min during the cigarette-smoking period (10). Therefore, it is highly probable that cigarette smoking inhibits pulsatile LH secretion in male nonsmokers.

Another important finding in the present study was that the inhibitory effect of a nicotine patch on the pulsatile LH secretion was not seen in female nonsmokers; Nicotinell TTS 10 (17.5 mg nicotine) did not inhibit the pulsatile LH secretion during the follicular phase of the menstrual cycle. Together with a previous report that cigarette smoking did not inhibit LH pulsatility in female nonsmokers at the late follicular phase (5), this result strongly suggests the presence of a sex difference in the response to nicotine, although we cannot deny the possibility that the nicotine effect would have been detected in females if more subjects had been studied. The mechanism for this sex difference was not ascertained in the present study, but it may be somehow related to differential roles of GABA in the control of pulsatile LH secretion between males and females. That is, for the control of pulsatile LH secretion, GABA neurons play a major role in male rats, mediating the negative feedback action of testosterone (24), whereas GABA neurons play only a minor role in female rats (25, 26) and opioid neurons mediate the negative feedback action of estrogen (27, 28). Taken together with our in vitro study suggesting that inhibitory nicotine effects on the GnRH pulse generator in the cultured rat embryonic olfactory placode appear via the stimulation of the release of inhibitory GABA (4) from GABA neurons existing in the same olfactory placode (26), the present result in male nonsmokers suggests that nicotine acts on GABA neurons to inhibit the activity of GnRH pulse generator present in the human hypothalamus (30).

In study 2 done to observe nicotine effects on the pulsatile LH secretion in male smokers, neither the interval nor the amplitude of the pulsatile LH secretion responded to the nicotine patch, i.e. nicotine’s inhibition of the pulsatile LH secretion was no longer observed, suggesting that tolerance to hypothalamic actions of nicotine had developed in our chronic male smokers. In the previous studies done to see the effect of cigarette smoking on LH secretion in male smokers, nicotine was ineffective on LH secretion in two studies (6, 11) in accord with ours, whereas it increased the serum LH level within 14 min after starting cigarette-smoking period of 12 min (10). The reason for the difference between our result and the latter is obscure, but it probably relates to the fact that we used Nicotinell TTS 10 that elevates nicotine concentration in blood to only about 4 ng/ml, whereas the latter study used cigarette smoking that elevates the nicotine level rapidly to about 20 ng/ml.

Although a considerable number of studies have dealt with the effect of smoking on male fertility, the available data do not conclusively demonstrate that smoking decreases male fertility (see review in Ref. 31). Sperm concentrations, motility, and/or morphology are often reduced, compared with results observed in nonsmokers, but they often remain within the normal range (see review in Ref. 32). Testosterone levels in blood are either decreased (33, 34) or increased (35, 36, 37) in male smokers. Finally, LH levels in blood are not significantly different between male nonsmokers and smokers (34, 35, 36). Thus, the present study is the first to demonstrate the decreased LH level in blood in male smokers, although testosterone levels were not changed. The reason previous studies did not find a decrease in male smokers may be related to the frequency of blood sampling from individual subjects: in two studies only one time and in another only three times. Because LH secretion is pulsatile, this sampling frequency may be too small to obtain the exact release level. Therefore, if deleterious effects of smoking on male fertility were discerned in male smokers, the decreased LH secretion may be a factor involved. However, the result should be interpreted with caution because the decrease in LH secretion was not associated with testosterone levels as stated above, even though a discrepancy between changes in LH levels and testosterone levels in smokers was evident in previous studies (35, 36, 37). Importantly, regulatory effects of LH on testosterone secretion are not simply related to the amount of LH or LH pulse frequency (38).

A number of studies has demonstrated that nicotine induces tolerance to many of its acute effects in humans (39, 40). However, it has been controversial how quickly this chronic tolerance is lost after cessation of nicotine exposure, i.e. quitting smoking. There are reports describing a rapid (within several days) loss of tolerance to the cardiovascular effect of nicotine (41, 42). But 1 yr after quitting, tolerance to the dysphoric effect of nicotine was modestly maintained (43), whereas tolerance to the subjective and reinforcing effect of nicotine was completely lost (44), suggesting that tolerance loss may be response specific. However, more recently no clear loss of tolerance was observed in any cardiovascular, subjective, and reinforcing effects of nicotine 3 wk after quitting cigarette smoking (45). The present results showed that, in male smokers, tolerance to the inhibitory effect on LH secretion might disappear within 1 wk. We therefore suggest that tolerance to nicotine is relatively easy to disappear if pulsatile LH secretion is checked as a target of nicotine effects.

Like female nonsmokers who showed no changes in pulsatile LH secretion in response to a transdermal nicotine patch, pulsatile LH secretion in female smokers also did not show responses to a transdermal nicotine patch. This seems somewhat surprising in light of reports that cigarette smoking has adverse effects on female fertility (31). However, as suggested previously (5), the antifertility effect of cigarette smoking in females may be mediated by mechanisms other than effects on the hypothalamus-pituitary system. For instance, cigarette smoking has been shown to reduce the ovarian reserve and lead to poor response to ovarian stimulation (29). However, because the latter authors documented that female smokers had a higher mean serum FSH concentration, the measurement of FSH in this series of studies may provide an answer.


   Footnotes
 
This work was supported by a Smoking Research Foundation grant for biochemical research.

First Published Online May 3, 2005

Abbreviations: CV, Coefficient of variation; GABA, {gamma}-aminobutyric acid; TTS, transdermal therapeutic system.

Received January 7, 2005.

Accepted April 25, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Blake CA 1974 Parallelism and divergence in luteinizing hormone and follicle-stimulating hormone release in nicotine-treated rats. Proc Soc Exp Biol Med 145:716–720[CrossRef][Medline]
  2. Sano A, Funabashi T, Kawaguchi M, Shinohara K, Kimura F 1999 Intravenous injections of nicotine decrease the pulsatile secretion of LH by inhibiting the gonadotropin-releasing hormone (GnRH) pulse generator activity in female rats. Psychoneuroendocrinology 24:397–407[CrossRef][Medline]
  3. Kimura F, Nishihara M, Hiruma H, Funabashi T 1991 Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats. Neuroendocrinology 53:97–102[Medline]
  4. Kimura F, Shinohara K, Funabashi T, Daikoku S, Suyama K, Mitsushima D, Sano A 2004 Nicotine inhibition of pulsatile GnRH secretion is mediated by GABAA receptor system in the cultured rat embryonic olfactory placode. Psychoneuroendocrinology 29:749–756[CrossRef][Medline]
  5. Thomas EJ, Edridge W, Weddell A, McGill A, McGarrigle HHG 1993 The impact of cigarette smoking on the plasma concentrations of gonadotrophins, ovarian steroids and androgens and upon the metabolism of oestrogens in the human female. Hum Reprod 8:1187–1193[Abstract/Free Full Text]
  6. Winternitz WW, Quillen D 1977 Acute hormonal response to cigarette smoking. J Clin Pharmacol 17:389–397[Abstract]
  7. Sandberg H, Roman L, Zavodnick J, Kupers N 1973 The effect of smoking on serum somatotropin, immunoreactive insulin and blood glucose levels of young adult males. J Pharmacol Exp Ther 184:787–791[Abstract/Free Full Text]
  8. Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME 1982 Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Psychopharmacology 78:305–308[CrossRef][Medline]
  9. Chiodera P, Volpi R, Capretti L, Speroni G, Necchi-Ghiri S, Caffarri G, Colla R, Coiro V 1997 Abnormal effect of cigarette smoking on pituitary hormone secretions in insulin-dependent diabetes mellitus. Clin Endocrinol (Oxf) 46:351–357[CrossRef][Medline]
  10. Mendelson JH, Sholar MB, Mutshler NH, Jaszyna-Gasior M, Goletiani NV, Siegel AJ, Mello NK 2003 Effects of intravenous cocaine and cigarette smoking on luteinizing hormone, testosterone, and prolactin in men. J Pharmacol Exp Ther 308:339–348
  11. Seyler Jr L, Pomerleau OF, Fertig JB, Hunt D, Parker K 1986 Pituitary hormone response to cigarette smoking. Pharmacol Biochem Behav 24:159–162[CrossRef][Medline]
  12. Brinkman GL, Coates EO 1963 The effect of bronchitis, smoking, and occupation on ventilation. Ann Rev Respir Dis 87:68–93
  13. He D, Funabashi T, Sano A, Uemura T, Minaguchi H, Kimura F 1999 Effects of glucose and related substrates on the recovery of the electrical activity of gonadotropin-releasing hormone pulse generator which is decreased by insulin-induced hypoglycemia in the estrogen-primed ovariectomized rat. Brain Res 820:71–76[CrossRef][Medline]
  14. Veldhuis JD, Johnson ML 1986 Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol 250:E486–E493
  15. Gallo RV 1981 Pulsatile LH release during the ovulatory LH surge on proestrus in the rat. Biol Reprod 24:100–104[Abstract]
  16. Funabashi T, Kato A, Kimura F 1990 Naloxone affects the luteinizing hormone secretory pattern in the short- and long-term ovariectomized rat. Neuroendocrinology 52:35–41[Medline]
  17. Nankin HR, Troen P 1971 Repetitive luteinizing hormone elevations in serum of normal men. J Clin Endocrinol Metab 33:558–560[Abstract/Free Full Text]
  18. Matsumoto AM, Bremner WJ 1984 Modulation of pulsatile gonadotropin secretion by testosterone in man. J Clin Endocrinol Metab 58:609–614[Abstract/Free Full Text]
  19. Yen SSC, Tsai CC, Naftolin F, Vandenberg G, Ajabor L 1972 Pulsatile patterns of gonadotropin release in subjects with and without ovarian function. J Clin Endocrinol Metab 34:671–675[Abstract/Free Full Text]
  20. Reame H, Sauder SE, Kelch RP, Marchall JC 1984 Pulsatile gonadotropin secretion during the human menstrual cycle: evidence for altered frequency of gonadotropin-releasing hormone secretion. J Clin Endocrinol Metab 559:328–337
  21. Filicori M, Santoro N, Merrriam GR, Crowley Jr WF 1986 Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle. J Clin Endocrinol Metab 62:1136–1144[Abstract/Free Full Text]
  22. Benowitz NL, Chan K, Denaro CP, Jacob III P 1991 Stable isotope method for studying transdermal drug absorption: the nicotine patch. Clin Pharmacol Ther 50:286–293[Medline]
  23. Isaac PF, Rand MJ 1972 Cigarette smoking and plasma levels of nicotine. Nature 236:308–310[CrossRef][Medline]
  24. Tin-Tin-Win-Shwe, Mitsushima D, Kimura F 2002 Profiles of in vivo {gamma}-aminobutyric acid release in the medial preoptic area of intact and castrated male rats. Neuroendocrinology 76:290–296[CrossRef][Medline]
  25. Kimura F, Sano A, Hiruma H, Funabashi T 1993 Effects of {gamma}-aminobutyric acid-A receptor antagonist, bicuculline, on the electrical activity of luteinizing hormone-releasing hormone pulse generator in the ovariectomized rat. Neuroendocrinology 57:605–614[Medline]
  26. Funabashi T, Daikoku S, Suyama K, Mitsushima D, Sano A, Kimura F 2002 Role of {gamma}-aminobutyric acid neurons in the release of gonadotropin-releasing hormone in cultured rat embryonic olfactory placodes. Neuroendocrinology 76:193–202[CrossRef][Medline]
  27. Kato A, Hiruma H, Kimura F 1994 Acute estradiol modulation of electrical activity of the LHRH pulse generator in the ovariectomized rat: restoration by naloxone. Neuroendocrinology 59:426–431[Medline]
  28. Kimura F, Funabashi T 1998 Two subgroups of gonadotropin-releasing hormone neurons control gonadotropin secretion in rats. News Physiol Sci 13:225–231[Abstract/Free Full Text]
  29. EI-Nemr A, AI-Shawaf T, Sabatini L, Wilson C, Lower AM, Grudzinskas JG 1998 Effect of smoking on ovarian reserve and ovarian stimulation in in vitro fertilization and embryo transfer. Hum Reprod 13:2192–2198[Abstract/Free Full Text]
  30. Knobil E 1980 The neuroendocrine control of the menstrual cycle. Rec Prog Horm Res 36:53–88
  31. The practice committee of the American Society for Reproductive Medicine 2004 Smoking and infertility. Fertil Steril 81:1181–1186[CrossRef][Medline]
  32. Vine MF 1996 Smoking and male reproduction: a review. Int J Androl 19:323–337[Medline]
  33. Briggs MH 1973 Cigarette smoking and infertility in men. Med J Australia 1:616–617
  34. Shaarawy M, Mahmoud KZ 1982 Endocrine profile and semen characteristics in male smokers. Fertil Steril 38:255–257[Medline]
  35. Andersen AN, Semczuk M, Tabor A 1984 Prolactin and pituitary-gonadal function in cigarette smoking infertile patients. Andrologia 16:391–396[Medline]
  36. Vogt H-J, Heller W-D, Borelli S 1986 Sperm quality of healthy smokers, ex-smokers, and never-smokers. Fertil Steril 45:106–110[Medline]
  37. Trummer H, Habermann H, Haas J, Pummer K 2002 The impact of cigarette smoking on human semen parameters and hormones. Hum Prod 17:1554–1559
  38. Hakola K, Pierroz DD, Aebi A, Vuagnat BAM, Aubert ML, Huhtaniemi I 1998 Dose and time relationships of intravenously injected rat recombinant luteinizing hormone and testicular testosterone secretion in the male rat. Biol Reprod 59:338–343[Abstract/Free Full Text]
  39. Arcavi L, Jacob III P, Hellerstein M, Benowitz NL 1994 Divergent tolerance to metabolic and cardiovascular effects of nicotine in smokers with low and high levels of cigarette consumption. Clin Pharmacol Ther 56:55–64[Medline]
  40. Foulds J, Stapleton JA, Bell N, Swettenham J, Jarvis MJ, Russell AH 1997 Mood and physiological effects of subcutaneous nicotine in smokers and never-smokers. Drug Alcohol Depend 44:105–115[CrossRef][Medline]
  41. Lee BL, Benowitz NL, Jacob III P 1987 Influence of tobacco abstinence on the disposition kinetics and effects of nicotine. Clin Pharmacol Ther 41:474–479.[Medline]
  42. Pomerleau OF, Pomerleau CS, Marks JL 2000 Abstinence effects and reactivity to nicotine during 11 days of smoking deprivation. Nicotine Tob Res 2:149–157[Abstract]
  43. Hughes JR, Strickler G, King D, Higgins ST, Fenwick JW, Gulliver SB, Mireault G 1989 Smoking history, instructions and the effects of nicotine: two pilot studies. Pharmacol Biochem Behav 34:149–155[CrossRef][Medline]
  44. Hughes JR, Rose GL, Gallas PW 2000 Do former smokers respond to nicotine differently from never smokers? A pilot study. Nicotine Tob Res 2:255–262[Abstract]
  45. Perkins KA, Gerlach D, Broge M, Sanders M, Grove J, Fonte C, Cherry C, Wilson A, Jacob R 2001 Quitting cigarette smoking produces minimal loss of chronic tolerance to nicotine. Psychopharmacology 158:7–17[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Alcohol AlcoholHome page
M. WALTER, U. GERHARD, M. GERLACH, H.-G. WEIJERS, J. BOENING, and G. A. WIESBECK
CONTROLLED STUDY ON THE COMBINED EFFECT OF ALCOHOL AND TOBACCO SMOKING ON TESTOSTERONE IN ALCOHOL-DEPENDENT MEN
Alcohol Alcohol., January 1, 2007; 42(1): 19 - 23.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. M. Lambert-Messerlian and B. L. Harlow
The Influence of Depression, Body Mass Index, and Smoking on Serum Inhibin B Levels in Late Reproductive-Aged Women
J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1496 - 1500.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Funabashi, T.
Right arrow Articles by Kimura, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Funabashi, T.
Right arrow Articles by Kimura, F.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Female Endocrinology
Right arrow Male Endocrinology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals