When Does Negative Feedback Mechanism For Hypothalamic-pituitary-gonadal Axis First Functional In Humans?

Posted on Tue, 26 Nov 2013

Question: Hi, I'm interested to know when does the negative feedback mechanism for hypothalamic-pituitary-gonadal axis first functional in humans? I ask because i underwent oxandrolone therapy at 14.5 years old, and its possible this suppresed my endogonous hormones. And concerned if this was the 'first' time my HPG got ' negative feedbacked'. Awaiting your advice. Regards

Answered by Dr. Praveen (2 hours later)

Brief Answer: Negative feedback is a normal phenomenon Detailed Answer: Hi. Thanks for writing on XXXXXXX Hypothalamo-adenal-gonadal (HPA) is responsible for the regulation of hormonal (steroid) levels in the body. Most of these steroids are controlled by negative feedback mechanism which means when the steroid (endogenous) levels are adequate this will results in decreased levels of hormones due to the inhibition of HPA axis and when the steroid levels fall below the normal levels the axis resets(gets activated) to maintain normal levels. Whenever steroids(exogenous -oxandralone etc) are given (exogenous) the body perceives that there are adequate hormonal levels and gradually (over weeks) HPA ceases to release/function. However the axis becomes active once the steroid(exogenous) is withdrawn gradually over weeks(2-8 weeks). I hope this helps.

Above answer was peer-reviewed by : Dr. Vaishalee Punj

Follow up: Dr. Praveen (40 minutes later)

Thank you doctor. So how can we prove negative feedback is mediated through androgen receptor for exogenous testosterone? As it's possible testosterone's negative feedback is mediated through its conversion to estrogen??

Answered by Dr. Praveen (10 hours later)

Brief Answer: By radionuclide/radioisotope imaging studies Detailed Answer: Hi. This molecular mechanism is evident at the level of hypothalamus (hypothalamic receptors) with the help of imaging techniques (radionuclide isotopes) targeted to androgen receptors. Although part of negative feedback of testosterone is mediated through extrogen & mostly by testosterone levels, Sex Hormone Binding Globulin (SHBG) also regulates the sex hormone levels. Hope this answers your question. Do write to us for further queries. Take care

Above answer was peer-reviewed by : Dr. Prasad

Follow up: Dr. Praveen (11 hours later)

Thank you Dr XXXXXXX I'd like to ask about possibilities of steroids having a stimulatory effect on gnrh pulse generator and pituitary gland. Traditionally, we understand outside sex steroids have 'negative feedback' on the endogonous levels. But suppose there is NO endogonous circulating levels to start with ie it's 0. And then sex steroids is given. In above scenario, would this 'outside sex steroid' have stimulatory effect on gnrh generator to start producing gnrh? Thank you if you can help. Wishing you all the best

Answered by Dr. Praveen (2 hours later)

Brief Answer: Steroid are a part of replacement therapy. Detailed Answer: Hi. Welcome back, Exogenous steroids form a part of replacement therapy that is they replenish/fill in the deficiency. Sex steroids(exogenous)/none of exogenous steroids stimulate the pituitary/hypothalamus. Depending on the viability and the functionality of hypothalamus/pituitary/adrenal/sex organs (assessed by various tests) hormone replacement/substitution therapy is initiated. There is nothing like a GnRH generator. Commercial preparations like GnRH agonists and antagonists are available. When hypothalamus(or pituitary/adrenal) is functioning adequately such GnRH analogues might not have the desired effect. Hope this answers your question. Thanks for writing to us. Kindly rate and keep us posted for further queries.

Above answer was peer-reviewed by : Dr. Yogesh D

Follow up: Dr. Praveen (22 hours later)

Thank you Dr XXXXXXX for your answers. I have one final query regarding leptin. How does the brain know about leptin levels in the body....is there communication system? Wishing you all the best.

Answered by Dr. Praveen (17 hours later)

Brief Answer: Brain senses leptin through hypothalamus Detailed Answer: Hypothalamus(neurons) is area which senses leptin levels.Leptin regulates reproductive, thyroid, growth hormone & energy balance(fed & fasting states).Hope this answers your question.Thanks for writing on XXXXXXX

Above answer was peer-reviewed by : Dr. Shanthi.E

Follow up: Dr. Praveen (3 hours later)

Thak you Dr XXXXXXX If i may i forgot to ask one more thing. In delayed puberty boys treated with oxandrolone, their hormones decreased during treatment but then 'rebounded higher' after the treatment. Does this mean the higher levels is now the 'new normal'? And if its sustained, does this mean oxandrolone, in a way, matured the hpg axis?? Best Regards, XXXXX

Answered by Dr. Praveen (1 hour later)

Brief Answer: Oxandralone does not help in maturation of HPA Detailed Answer: Hi. Oxandralone when used in delayed puberty helps in development of secondary sexual characters.Once the HPA is matured Oxandralone can b gradually withdrawn if the hormonal levels are high(else it might result in hyperandrogenism).Gradual withdrawal can be done on restoration of HPA.Oxandralone is used only for substitution not for stimulation of HPA.I hope I have answered.your query. Thanks for writing to us on XXXXXXX

Above answer was peer-reviewed by : Dr. Prasad

Follow up: Dr. Praveen (15 minutes later)

Thank you Dr XXXXXXX for the answer. Its reported the following interact with each other during onset of Gnrh pulse generator: Kisspeptins Leptin Glutamate Gamma-aminobutyric acid Neuropeptide Y After generator is working, does the 'progress' also depend on the above? Or is the above just important for the initial 'onset'?? Secondly, what is the explanation for 'rebound' effect after stopping oxandrolone in the above-mentioned patients?? Best Regards

Answered by Dr. Praveen (18 hours later)

Brief Answer: Endogenous peptides are responsible for both Detailed Answer: Hi. The peptides mentioned above are responsible for the regulation of the hypothalamus function - few of them are excitatory and few inhibitory & play an important role in initiation as well as continuation of the function (by various micro molecular mechanisms). Since the body is dependent on certain level of these hormones naturally it try to adapt once the exogenous steroid is stopped and achieves a new level gradually.If the body cannot cope up then it results in withdrawal effects/sometimes shock. Hope I have answered your queries.

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Above answer was peer-reviewed by : Dr. Vaishalee Punj